DE1171439B - Process for the preparation of salts of 4, 6-diamino-1, 2-dihydro-2-lower-alkyl-1-aryl-s-triazines with 4, 4'-methylene-bis- (3-hydroxy-2- naphthoic acid) - Google Patents
Process for the preparation of salts of 4, 6-diamino-1, 2-dihydro-2-lower-alkyl-1-aryl-s-triazines with 4, 4'-methylene-bis- (3-hydroxy-2- naphthoic acid)Info
- Publication number
- DE1171439B DE1171439B DEP28646A DEP0028646A DE1171439B DE 1171439 B DE1171439 B DE 1171439B DE P28646 A DEP28646 A DE P28646A DE P0028646 A DEP0028646 A DE P0028646A DE 1171439 B DE1171439 B DE 1171439B
- Authority
- DE
- Germany
- Prior art keywords
- hydroxy
- dihydro
- diamino
- methylene
- bis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000003839 salts Chemical class 0.000 title claims description 54
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 title claims description 34
- 238000000034 method Methods 0.000 title claims description 12
- 238000002360 preparation method Methods 0.000 title claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 230000005923 long-lasting effect Effects 0.000 claims description 3
- 201000004792 malaria Diseases 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
- DNQSGXVJKQBSMT-UHFFFAOYSA-L disodium;3-carboxy-1-[(3-carboxy-2-oxidonaphthalen-1-yl)methyl]naphthalen-2-olate;hydrate Chemical compound O.[Na+].[Na+].C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3[O-])C(=O)O)=C([O-])C(C(O)=O)=CC2=C1 DNQSGXVJKQBSMT-UHFFFAOYSA-L 0.000 description 25
- -1 amine salts Chemical class 0.000 description 23
- 238000001953 recrystallisation Methods 0.000 description 22
- 239000000243 solution Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 14
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 4
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 4
- 239000003430 antimalarial agent Substances 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 230000000078 anti-malarial effect Effects 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 2
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- QKDYRATUILIGIC-UHFFFAOYSA-N 4,4-dimethyl-1H-1,3,5-triazine hydrochloride Chemical compound Cl.CC1(NC=NC=N1)C QKDYRATUILIGIC-UHFFFAOYSA-N 0.000 description 2
- CXIUWTTYUPDMGW-UHFFFAOYSA-N 4,4-dimethyl-1h-1,3,5-triazine Chemical compound CC1(C)NC=NC=N1 CXIUWTTYUPDMGW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 229940033495 antimalarials Drugs 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- ZEOIMTZUCPVMBV-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-2-methyl-2h-1,3,5-triazine-4,6-diamine Chemical compound CC1N=C(N)N=C(N)N1C1=CC=C(Cl)C(Cl)=C1 ZEOIMTZUCPVMBV-UHFFFAOYSA-N 0.000 description 1
- IHKQPSLZKSGONB-UHFFFAOYSA-N 1-(3,5-dibromophenyl)-6,6-dimethyl-1,3,5-triazine-2,4-diamine Chemical compound BrC=1C=C(C=C(C=1)Br)N1C(N=C(N=C1N)N)(C)C IHKQPSLZKSGONB-UHFFFAOYSA-N 0.000 description 1
- FTQUITOMKYDIRQ-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)-6,6-dimethyl-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1C1=CC(Cl)=CC(Cl)=C1 FTQUITOMKYDIRQ-UHFFFAOYSA-N 0.000 description 1
- AXIUXECRTOGILY-UHFFFAOYSA-N 1-(3-chlorophenyl)-6,6-dimethyl-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1C1=CC=CC(Cl)=C1 AXIUXECRTOGILY-UHFFFAOYSA-N 0.000 description 1
- XHCUHVHWTQIMSO-UHFFFAOYSA-N 1-(3-chlorophenyl)-6,6-dimethyl-1,3,5-triazine-2,4-diamine;hydrochloride Chemical compound Cl.CC1(C)N=C(N)N=C(N)N1C1=CC=CC(Cl)=C1 XHCUHVHWTQIMSO-UHFFFAOYSA-N 0.000 description 1
- LYIAPCQBECZCGT-UHFFFAOYSA-N 1-(3-ethoxyphenyl)-6,6-dimethyl-1,3,5-triazine-2,4-diamine Chemical compound CCOC1=CC=CC(N2C(N=C(N)N=C2N)(C)C)=C1 LYIAPCQBECZCGT-UHFFFAOYSA-N 0.000 description 1
- IANXQZFGCPHWLQ-UHFFFAOYSA-N 1-(3-methoxyphenyl)-6,6-dimethyl-1,3,5-triazine-2,4-diamine Chemical compound COC1=CC=CC(N2C(N=C(N)N=C2N)(C)C)=C1 IANXQZFGCPHWLQ-UHFFFAOYSA-N 0.000 description 1
- LLRTYNPSGQWCLZ-UHFFFAOYSA-N 1-(4-bromophenyl)-6,6-dimethyl-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1C1=CC=C(Br)C=C1 LLRTYNPSGQWCLZ-UHFFFAOYSA-N 0.000 description 1
- JRPWIFUWNNYKIU-UHFFFAOYSA-N 1-(4-iodophenyl)-6,6-dimethyl-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1C1=CC=C(I)C=C1 JRPWIFUWNNYKIU-UHFFFAOYSA-N 0.000 description 1
- KLCSZLKQTXQCTD-UHFFFAOYSA-N 1-(4-methoxyphenyl)-6,6-dimethyl-1,3,5-triazine-2,4-diamine Chemical compound C1=CC(OC)=CC=C1N1C(C)(C)N=C(N)N=C1N KLCSZLKQTXQCTD-UHFFFAOYSA-N 0.000 description 1
- QYPYKZMBXDTOFR-UHFFFAOYSA-N 1-(4-methoxyphenyl)-6,6-dimethyl-1,3,5-triazine-2,4-diamine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1N1C(C)(C)N=C(N)N=C1N QYPYKZMBXDTOFR-UHFFFAOYSA-N 0.000 description 1
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
- QCBSYPYHCJMQGB-UHFFFAOYSA-N 2-ethyl-1,3,5-triazine Chemical compound CCC1=NC=NC=N1 QCBSYPYHCJMQGB-UHFFFAOYSA-N 0.000 description 1
- YIUOAAUFVBZQPM-UHFFFAOYSA-N 2-methyl-1,3,5-triazine Chemical compound CC1=NC=NC=N1 YIUOAAUFVBZQPM-UHFFFAOYSA-N 0.000 description 1
- ATIZMCQCSBZFEM-UHFFFAOYSA-N 2-methyl-1,3,5-triazine hydrochloride Chemical compound CC1=NC=NC=N1.Cl ATIZMCQCSBZFEM-UHFFFAOYSA-N 0.000 description 1
- UOBYKYZJUGYBDK-UHFFFAOYSA-N 2-naphthoic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
- YPMIMCWABMFCKU-UHFFFAOYSA-N 6,6-dimethyl-1-(4-methylphenyl)-1,3,5-triazine-2,4-diamine;hydrochloride Chemical compound Cl.C1=CC(C)=CC=C1N1C(C)(C)N=C(N)N=C1N YPMIMCWABMFCKU-UHFFFAOYSA-N 0.000 description 1
- GYXWUBHCYWWAOK-UHFFFAOYSA-N 6,6-dimethyl-1-(4-methylsulfanylphenyl)-1,3,5-triazine-2,4-diamine Chemical compound C1=CC(SC)=CC=C1N1C(C)(C)N=C(N)N=C1N GYXWUBHCYWWAOK-UHFFFAOYSA-N 0.000 description 1
- VMVKLCXTXSSZSI-UHFFFAOYSA-N 6,6-dimethyl-1-phenyl-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1C1=CC=CC=C1 VMVKLCXTXSSZSI-UHFFFAOYSA-N 0.000 description 1
- QDPFZWLLUCPLDI-UHFFFAOYSA-N 6,6-dimethyl-1-phenyl-1,3,5-triazine-2,4-diamine;hydrochloride Chemical compound Cl.CC1(C)N=C(N)N=C(N)N1C1=CC=CC=C1 QDPFZWLLUCPLDI-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- QBTCAQHLYVFRHS-UHFFFAOYSA-N Cl.NC1=NC(N(C(=N1)N)C1=CC(=C(C=C1)C)C)(C)C Chemical compound Cl.NC1=NC(N(C(=N1)N)C1=CC(=C(C=C1)C)C)(C)C QBTCAQHLYVFRHS-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- MOUAPRKJJUXEIE-UHFFFAOYSA-N cycloguanil hydrochloride Chemical compound Cl.CC1(C)N=C(N)N=C(N)N1C1=CC=C(Cl)C=C1 MOUAPRKJJUXEIE-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- BWAUQTFFVCLSOS-UHFFFAOYSA-N sodiosodium hydrate Chemical compound O.[Na].[Na] BWAUQTFFVCLSOS-UHFFFAOYSA-N 0.000 description 1
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/10—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
- C07D251/18—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom with nitrogen atoms directly attached to the two other ring carbon atoms, e.g. guanamines
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
DEUTSCHESGERMAN
PATENTAMTPATENT OFFICE
AUSLEGESCHRIFTEDITORIAL
Internat. Kl.: C 07 dBoarding school Class: C 07 d
Deutsche Kl.: 12 ρ -10/05 German class: 12 ρ - 10/05
Nummer:
Aktenzeichen:
Anmeldetag:
Auslegetag:Number:
File number:
Registration date:
Display day:
P 28646 IVd/12 ρ
22. Januar 1962
4. Juni 1964P 28646 IVd / 12 ρ
January 22, 1962
4th June 1964
Die Erfindung bezieht sich auf ein Verfahren zur Herstellung von Salzen von 4,6-Diamino-l,2-dihydro-2-niederalkyl-l-aryl-s-triazinen der FormelThe invention relates to a process for the preparation of salts of 4,6-diamino-1,2-dihydro-2-lower alkyl-1-aryl-s-triazines the formula
Verfahren zur Herstellung von gegen MalariaMethod of producing against malaria
langanhaltend wirksamen Salzen vonlong-lasting salts of
4,6-Diamino-1 ^-dihydro-^-niederalkyl-l-aryl-s-4,6-diamino-1 ^ -dihydro - ^ - lower alkyl-1-aryl-s-
triazinen mit 4,4'-Methylen-bis-(3-hydroxy-2-triazines with 4,4'-methylene-bis- (3-hydroxy-2-
naphthoesäure)naphthoic acid)
H2N,H 2 N,
NNNN
NH2 NH 2
in der X Wasserstoff, Halogen, eine Methyl- oder Trifluormethylgruppe und beide Y und Z Wasserstoff, Halogen, niedere Alkyl-, niedere Alkoxy-, niedere Alkylthio-, Trifluormethyl- oder Benzyloxygruppen bedeuten und mindestens eine der Gruppen X, Y und Z Wasserstoff ist und R1 eine niedere Alkylgruppe und R2 Wasserstoff oder eine Methylgruppe bedeutet, mit 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure) oder Pamoiiisäure der Formelin which X is hydrogen, halogen, a methyl or trifluoromethyl group and both Y and Z are hydrogen, halogen, lower alkyl, lower alkoxy, lower alkylthio, trifluoromethyl or benzyloxy groups and at least one of the groups X, Y and Z is hydrogen and R 1 is a lower alkyl group and R 2 is hydrogen or a methyl group, with 4,4'-methylenebis (3-hydroxy-2-naphthoic acid) or pamoic acid of the formula
CH2 CH 2
COOHCOOH
OHOH
OHOH
Anmelder:Applicant:
Parke, Davis & Company, Detroit, Mich.Parke, Davis & Company, Detroit, Mich.
(V. St. A.)(V. St. A.)
Vertreter:Representative:
Dr.-Ing. F. Wuesthoff, Dipl.-Ing. G. Puls und
Dipl.-Chem Dr. rer. nat. E. Frhr. v. Pechmann,
Patentanwälte, München 9, Schweigerstr. 2Dr.-Ing. F. Wuesthoff, Dipl.-Ing. G. Pulse and
Dipl.-Chem Dr. rer. nat. E. Frhr. v. Bad luck man,
Patent Attorneys, Munich 9, Schweigerstr. 2
Als Erfinder benannt:Named as inventor:
Edward Faith Eislager,Edward Faith Ice Storage,
Donald Francis Worth, Ann Arbor, Mich.Donald Francis Worth, Ann Arbor, Me.
(V. St. A.)(V. St. A.)
Beanspruchte Priorität:Claimed priority:
V. St. v. Amerika vom 23. Januar 1961 (83 909)V. St. v. America January 23, 1961 (83 909)
XCOOH X COOH
In den vorstehenden Definitionen bedeutet »Halogen« ein Fluor-, Chlor-, Brom- oder Jodatom, und die niederen Alkylreste sind solche, die weniger als 5 C-Atome enthalten.In the above definitions, "halogen" means a fluorine, chlorine, bromine or iodine atom, and the lower alkyl radicals are those which contain fewer than 5 carbon atoms.
Die erfindungsgemäß erhältlichen Salze werden in an sich bekannter Weise hergestellt, indem man in Gegenwart eines Lösungsmittels 1 Mol eines 4,6-Diamino-1 ^-dihydro^-niederalkyl-1 -aryl-s-triazins der vorstehenden Formel mit einem ganzen oder halben Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure) umsetzt; an Stelle der freien Base und Säure kann auch ein lösliches Salz von 4,6-Diamino-l,2-dihydro-2-niederalkyl-1-aral-s-triazin mit einem löslichen Salz von 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure) zur Reaktion gebracht werden.The salts obtainable according to the invention are prepared in a manner known per se by in Presence of a solvent 1 mole of a 4,6-diamino-1 ^ -dihydro ^ -lower alkyl-1-aryl-s-triazines der the above formula with a whole or half mole of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid) implements; Instead of the free base and acid, a soluble salt of 4,6-diamino-1,2-dihydro-2-lower-alkyl-1-aral-s-triazine can also be used with a soluble salt of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid) to react to be brought.
Der Begriff »lösliches Salz« wird hier in einem relativen Sinn verwendet und bedeutet eine Löslichkeit, die wesentlich größer ist als die der Produkte nach der Erfindung. Beispiele für lösliche Salze der Triazinbase, die für die Verwendung bei dem Verfahren der Erfindung geeignet sind, sind das Hydrochlorid, Hydrobromid, Hydrojodid, Sulfat, Phosphat, SuIfamat, Acetat, Lactat, Tartrat, Gluconat, Citrat und Salicylat. Beispiele für die löslichen Salze von 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure), die für die Verwendung bei dem Verfahren nach der Erfindung geeignet sind, sind die Alkali-, Erdalkali-, Ammonium- und Aminsalze. Dabei können sowohl die Ausgangsmaterialien als auch die Endprodukte in hydratisierter oder in wasserfreier Form vorliegen. Falls gewünscht, können die beim Verfahren verwendeten Ausgangsstoffe in situ in die gewünschte Base, Säure oder ein lösliches Salz übergeführt werden durch Behandlung mit einer Säure oder einer Base, z. B. durch Neutralisieren von einer oder mehreren Carboxylgruppen mit einer Base, durch Behandlung eines Carboxylates mitThe term "soluble salt" is used here in a relative sense and means a solubility which is much larger than that of the products according to the invention. Examples of soluble salts of the triazine base, which are suitable for use in the method of the invention are the hydrochloride, Hydrobromide, hydroiodide, sulfate, phosphate, sulfamate, Acetate, lactate, tartrate, gluconate, citrate and salicylate. Examples of the soluble salts of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid), which are suitable for use in the method according to the invention are the alkali, alkaline earth, ammonium and amine salts. Both the starting materials and the end products can be used in hydrated or in an anhydrous form. If desired, the starting materials used in the process can can be converted in situ into the desired base, acid or a soluble salt by treatment with an acid or a base, e.g. B. by neutralizing one or more carboxyl groups with a base, by treating a carboxylate with
409 598/437409 598/437
einer Mineralsäure, durch Behandlung eines Säureadditionssalzes mit einer Base oder durch Behandlung der Triazinbase mit einer Säure.a mineral acid, by treatment of an acid addition salt with a base or by treatment the triazine base with an acid.
Das Verfahren nach der Erfindung wird in einem Lösungsmittel durchgeführt, in dem die Reaktionsteilnehmer mindestens teilweise löslich sind und das wenig mit den Reaktionsteilnehmern reagiert. Geeignete Lösungsmittel sind z. B. Wasser, wäßrige Alkanole, Dimethylacetamid, Acetonitril und derenThe process according to the invention is carried out in a solvent in which the reactants are at least partially soluble and that Reacted little with the respondents. Suitable solvents are e.g. B. water, aqueous Alkanols, dimethylacetamide, acetonitrile and their
Sogar wenn sie in Intervallen von weniger als einer Woche verabreicht werden, werden diese Verbindungen zu schnell ausgeschieden, um eine dauernde Wirkung zu ergeben. Außerdem rufen sie bei der Injektion Reizerscheinungen hervor. Die Verfahrensprodukte nach vorliegender Erfindung besitzen nun eine hohe Antimalariawirksamkeit und zeigen bei einer Injektion keine Reizerscheinungen und üben eine solche lang andauernde Wirkung aus, so daß das Dosierungs-Even when given at intervals of less than a week, these compounds will excreted too quickly to give lasting effect. They also call for the injection Signs of irritation. The process products according to the present invention now have a high Antimalarial efficacy and show no irritation symptoms when injected and practice such a long time lasting effect, so that the dosage
Gemische. Weitere zufriedenstellende Reaktionsme- io intervall bis auf mehrere Monate gestreckt werden
dien können ausgewählt werden aus einer Vielzahl von kann ohne einen Verlust eines Schutzes gegen eine
Lösungsmitteln, insbesondere den neutralen und
polaren. Die Salzbildung verläuft beim VermischenMixtures. Further satisfactory reaction intervals can be extended to several months without a loss of protection against solvents, in particular the neutral ones
polar. Salt formation takes place during mixing
der Reaktionsteilnehmer in dem gewählten Lösungs-the reactants in the chosen solution
Malariainfektion. Die Produkte nach der Erfindung können zu Suspensionen zusammengestellt werden, die pharmazeutisch brauchbar sind für intramuskuläreMalaria infection. The products according to the invention can be put together to form suspensions, which are pharmaceutically useful for intramuscular
mittel ziemlich schnell. 15 Injektion unter Verwendung von Suspensionsträgern,medium pretty fast. 15 injection using suspension carriers,
Das Verfahren kann bei Raumtemperatur oder bei wie 40% Benzylbenzoat und 60% Ricinusöl oderThe process can be carried out at room temperature or at such as 40% benzyl benzoate and 60% castor oil or
tieferen Temperaturen durchgeführt werden, obgleich Wasser, das Emulgierungsmittel und Dispergierungsin vielen Fällen eine hohe Ausbeute und eine rasch mittel enthält.Lower temperatures can be carried out, although water, the emulsifying agent and dispersing agent in many cases a high yield and a quick medium contains.
filtrierbare, kristalline Form durch Erwärmen des Die Erfindung wird durch die nachstehenden Bei-filterable, crystalline form by heating the The invention is illustrated by the following
Reaktionsgemisches bis zu einer Stunde und an- 20 spiele erläutert, aber nicht begrenzt.Reaction mixture for up to an hour and examples are explained, but not limited.
schließendes Abkühlen begünstigt werden.subsequent cooling are favored.
Die Reaktionsteilnehmer werden gewöhnlich in dem gleichen Verhältnis angewendet, in dem sie in dem fertigen Endprodukt erscheinen. Falls man das SalzThe reactants are usually used in the same proportion as they are used in the finished end product appear. In case you have the salt
s-triazin mit V2 Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); gelbe Kristalle; F. 231 bis 234°C nach einer Umkristallisation aus einem Gemisch aus Dimethylsulfoxyd und Wasser. Die Strukturformel ists-triazine with V2 moles of 4,4'-methylenebis (3-hydroxy-2-naphthoic acid); yellow crystals; F. 231 to 234 ° C after recrystallization from a mixture of Dimethyl sulfoxide and water. The structural formula is
ClCl
COOHCOOH
Eine Lösung von 19,7 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat in der Triazinbase mit einem halben Mol 4,4'-Methylen- 25 500 ecm Wasser wird unter kräftigem Rühren in eine bis-(3-hydroxy-2-naphthoesäure) zu erhalten wünscht, Lösung von 25,2 g 4,6-Diamino-l-(p-chlorphenyl)-verwendet man gewöhnlich die Reaktionsteilnehmer l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid oder deren lösliche Salze im Verhältnis von 2 Mol des in 500 ecm heißem Wasser gegossen. Das Gemisch erstgenannten bis zu 1 Mol des letztgenannten. Wenn wird gerührt und auf dem Dampfbade 15 Minuten man das Salz der Triazinbase mit einem ganzen Mol 30 erwärmt, und das sich abscheidende unlösliche Pro-4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure) zu er- dukt wird auf einem Filter gesammelt, mit Wasser halten wünscht, werden beste Ergebnisse erzielt durch gewaschen und im Vakuum 18 Stunden bei 700C Umsetzung eines löslichen Salzes der Triazinbase mit getrocknet. Dieses Produkt ist das Salz aus 4,6-Dieiner äquimolekularen Menge eines löslichen Salzes, amino-l-(p-chlorphenyl)-l,2-dihydro-2,2-dimethylz. B. des Dinatriumsalzes, von 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure), in Gegenwart eines Äquivalentes einer Mineralsäure.A solution of 19.7 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate in the triazine base with half a mole of 4,4'-methylene 25 500 ecm of water is vigorously Stirring in a bis (3-hydroxy-2-naphthoic acid) desires to obtain a solution of 25.2 g of 4,6-diamino-1- (p-chlorophenyl) - one usually uses the reactants 1,2-dihydro-2 , 2-dimethyl-s-triazine monohydrochloride or its soluble salts in a ratio of 2 mol of that poured into 500 ecm of hot water. The mixture of the former up to 1 mole of the latter. If it is stirred and heated on the steam bath for 15 minutes, the salt of the triazine base is heated to a whole mol, and the insoluble pro-4,4'-methylenebis (3-hydroxy-2-naphthoic acid) which separates out is produced is collected on a filter, wishes it with water, best results are achieved by and dried in vacuo for 18 hours at 70 0 C. reacting a soluble salt of the Triazinbase with dried. This product is the salt of 4,6-di-an equimolecular amount of a soluble salt, amino-1- (p-chlorophenyl) -l, 2-dihydro-2,2-dimethylz. B. the disodium salt of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid), in the presence of one equivalent of a mineral acid.
Wenn das Reaktionsprodukt direkt ausfällt, wird es durch Zentrifugieren oder Filtrieren isoliert. Wenn es nicht direkt ausfällt, wird es zunächst durch Einengen des Reaktionsgemisches oder durch Verdünnen des Reaktionsgemisches mit einem Lösungsmittel, in dem das Produkt unlöslich ist, ausgefällt und dann gewonnen.If the reaction product precipitates outright, it is isolated by centrifugation or filtration. if if it does not precipitate directly, it is first obtained by concentrating the reaction mixture or by diluting it the reaction mixture is precipitated with a solvent in which the product is insoluble and then won.
Die 4,6-Diamino-l,2-dihydro-2-niederalkyl-l-aryls-triazine und ihre löslichen Salze, wie sie als Ausgangsmaterialien verwendet werden bei der Durchführung der Erfindung, sind bekannt und können auf zahlreichen Wegen hergestellt werden. Die erfindungsgemäß hergestellten Produkte zeigenThe 4,6-diamino-1,2-dihydro-2-lower alkyl-1-aryls-triazines and their soluble salts, as used as starting materials for use in practicing the invention are known and can be used in numerous ways Because of being made. The products produced according to the invention show
eine außergewöhnlich lang andauernde Wirkung. Diejenigen Verbindungen, die in 3- und 5-Stellung des Phenylrings substituiert sind, d. h. die Verbindungen, in denen Y Wasserstoff ist und X und Z andere Sub-an exceptionally long-lasting effect. Those compounds which are in the 3- and 5-position des Phenyl rings are substituted, d. H. the compounds in which Y is hydrogen and X and Z other sub-
stituenten, vorzugsweise Halogen, Methyl oder Tri- 55 nachstehend angegebenen Reagenzien können die fluormethyl sind, sind besonders wertvoll als Depot- nachstehenden, weiteren Verbindungen hergestelltsubstituents, preferably halogen, methyl or tri 55 specified below reagents can Fluoromethyl are particularly valuable as depot- the following, other compounds are made
Antimalariamittel. Diejenigen Produkte nach der Erfindung, die in dem Phenylring nicht substituiert sind oder nur an einer der beiden Stellungen 3 oder 4 Substituenten haben, entsprechend den Substituenten Y und Z, werden in erster Linie als Antimalariadepotmittel verwendet. Es ist zwar eine Reihe von Verbindungen, wie4,6-Diamino-l-(p-chlorphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-hydrochlorid undAntimalarials. Those products according to the invention which are not substituted in the phenyl ring are or only have 3 or 4 substituents in one of the two positions, corresponding to the substituents Y and Z, are used primarily as antimalarial depots. It is a series though of compounds such as 4,6-diamino-1- (p-chlorophenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine hydrochloride and
4,6-Diamino-l-(3,4-dichlorphenyl)-l,2-dihydro-2,2-di- 65 s-triazin mit V2MoI4,6-diamino-1- (3,4-dichlorophenyl) -1, 2-dihydro-2,2-di-65 s-triazine with V 2 mol
methyl-s-triazin-hydrochlorid, als hochwirksame Anti- 2-naphthoesäure); F.methyl-s-triazine hydrochloride, as a highly effective anti-2-naphthoic acid); F.
malariamittel bekannt, doch ist ihre Verwendbarkeit durch ihre nur kurz anhaltende Wirkung begrenzt.known to be anti-malarials, but their usefulness is limited by their short-term effects.
HaNH a N
N NN N
NH,NH,
CH3 CH 3
CH3 CH 3
CH,CH,
OHOH
OHOH
COOHCOOH
Nach der vorstehenden Arbeitsweise und mit denAccording to the above procedure and with the
werden. In Abhängigkeit von dem verwendeten Trockenverfahren werden sie entweder als Hydrate oder in wasserfreier Form erhalten.will. Depending on the dry process used, they are either called hydrates or obtained in anhydrous form.
a) Aus 1,50 g 4,6-Diamino-l-(m-fluorphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid und 1,24 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatrium-monohydrat erhält man das Salz aus 4,6-Diamino-1 -(m-fluorphenyl)-1,2 -dihydro -2,2 -dimethyl 4,4'-Methylen-bis-(3-hydroxy- unbestimmt, beginnend bei 190°C nach einer Umkristallisation aus Methanol und Wasser.a) From 1.50 g of 4,6-diamino-1- (m-fluorophenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine monohydrochloride and 1.24 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium monohydrate, the salt of 4,6-diamino-1 is obtained - (m-fluorophenyl) -1,2-dihydro -2,2 -dimethyl 4,4'-methylene-bis- (3-hydroxy- undetermined, starting at 190 ° C after recrystallization from methanol and Water.
b) Aus 2,50 g 4,6-Diamino-l-(m-chlorphenyl)- 1,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid und 1,96 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz aus 4,6 - Diamino -1 - (m - chlorphenyl) -1,2 - dihydro -2,2-dimethyl-s-triazin mit Va MoI 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. unbestimmt, beginnend bei 1900C nach einer Umkristallisation aus Methanol und Wasser.b) From 2.50 g of 4,6-diamino-l- (m-chlorophenyl) - 1,2-dihydro-2,2-dimethyl-s-triazine monohydrochloride and 1.96 g of 4,4'-methylene bis- (3-hydroxy-2-naphthoic acid) disodium salt monohydrate is obtained from the salt of 4,6-diamino -1- (m-chlorophenyl) -1,2-dihydro-2,2-dimethyl-s-triazine with Va MoI 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid); F. undetermined, starting at 190 ° C. after recrystallization from methanol and water.
c) Aus 9,00 g4,6-Diamino-l-(m-bromphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid und 6,08 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz aus 4,6-Diamino-l-(m-bromphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin mit 1I2 Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. unbestimmt, beginnend bei 180°C.c) From 9.00 g of 4,6-diamino-1- (m-bromophenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine monohydrochloride and 6.08 g of 4,4'-methylene-bis - (3-hydroxy-2-naphthoic acid) disodium salt monohydrate, the salt is obtained from 4,6-diamino-1- (m-bromophenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine with 1 I 2 moles of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid); F. indeterminate, starting at 180 ° C.
d) Aus 10,00 g 4,6-Diamino-1,2-dihydro-2,2-dimethyl-1-phenyl-s-triazin-monohydrochlorid und 8,86 g 4,4' - Methylen - bis - (3 - hydroxy - 2 - naphthoesäure) - di natriumsalz-monohydrat erhält man das Salz aus 4,6-Diamino-1,2-dihydro-2,2-dimethyl-1 -phenyl-s-triazin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. unbestimmt, beginnend bei 2000C nach einer Umkristallisation aus Methanol und Wasser.d) From 10.00 g of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-phenyl-s-triazine monohydrochloride and 8.86 g of 4,4'-methylene-bis (3 - hydroxy - 2 - naphthoic acid) - disodium salt monohydrate, the salt is obtained from 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-phenyl-s-triazine with Va mol 4,4'- Methylene bis (3-hydroxy-2-naphthoic acid); F. undetermined, starting at 200 ° C. after recrystallization from methanol and water.
e) Aus 6,00 g 4,6-Diamino-l,2-dihydro-l-(rn-methoxyphenyl) - 2,2- dimethyl - s - triazin - monohydrochlorid und 4,76 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz aus 4,6-Diamino-l,2-dihydro-l-(m-methoxyphenyl)-2,2-dimethyl-s-triazin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. unbestimmt, beginnend bei 205° C nach einer Umkristallisation aus Methanol und Wasser.e) From 6.00 g of 4,6-diamino-1,2-dihydro-1- (rn-methoxyphenyl) -2,2-dimethyl-s-triazine-monohydrochloride and 4.76 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate the salt is obtained from 4,6-diamino-1,2-dihydro-1- (m-methoxyphenyl) -2,2-dimethyl-s-triazine with Va moles of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid); F. undetermined, starting at 205 ° C after recrystallization Methanol and water.
f) Aus 9,00 g 4,6-Diamino-l-(m-äthoxyphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid und 7,75 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz aus 4,6 - Diamino -1 - (m - äthoxyphenyl) -1,2 - dihydro 2,2-dimethyl-s-triazin mit V2 Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. unbestimmt, beginnend bei 175° C nach einer Umkristallisation aus Äthanol und Wasser.f) From 9.00 g of 4,6-diamino-1- (m-ethoxyphenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine monohydrochloride and 7.75 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate the salt is obtained from 4,6 - diamino -1 - (m - ethoxyphenyl) -1,2 - dihydro 2,2-dimethyl-s-triazine with V2 moles of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid); F. undetermined, starting at 175 ° C after recrystallization Ethanol and water.
g) Aus 6,5 g 4,6-Diamino-l-(p-äthoxyphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid und 4,90 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz aus 4,6-Diamino-l-(p-äthoxyphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin mit V2M0I 4,4'-Methylen-bis-(3-hy-1830C nach einer Umkristallisation aus Acetonitril und Wasser.g) From 6.5 g of 4,6-diamino-l- (p-ethoxyphenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine monohydrochloride and 4.90 g of 4,4'-methylene bis- (3-hydroxy-2-naphthoic acid) disodium salt monohydrate is obtained from the salt of 4,6-diamino-1- (p-ethoxyphenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine with V2M0I 4,4'-methylene-bis- (3-hy-183 0 C after recrystallization from acetonitrile and water.
j) Aus 12,9 g 4,6-Diamino-l-(3,4-dichlorphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid und 9,0 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz aus 4,6-Diamino-l-(3,4-dichlorphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. unbestimmt, beginnend bei 213°C nach einer Umkristallisation aus Acetonitril und Wasser.j) From 12.9 g of 4,6-diamino-1- (3,4-dichlorophenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine monohydrochloride and 9.0 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate the salt is obtained from 4,6-diamino-1- (3,4-dichlorophenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine with Va moles of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid); F. indefinite, beginning at 213 ° C after recrystallization Acetonitrile and water.
k) Aus 15,2 g 4,6-Diamino-l-(p-jodphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid und 9,0 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz aus 4,6-Diamino- l-(p-jodphenyl)-1,2-dihydro-2,2-dimethyl-s-triazin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. 2120C unter Zersetzung nach einer Umkristallisation aus Acetonitril und Wasser. 1) Aus 5,0 g 4,6-Diamino-l-(p-bromphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid und 3,38 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz aus 4,6-Diamino-1 -(p-bromphenyl)-1,2-dihydro-2,2-dimethyl-s-triazin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure; chartreusefarbige Kristalle; F. 230 bis 235°C.k) From 15.2 g of 4,6-diamino-l- (p-iodophenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine monohydrochloride and 9.0 g of 4,4'-methylene bis- (3-hydroxy-2-naphthoic acid) disodium salt monohydrate is obtained from the salt of 4,6-diamino-1- (p-iodophenyl) -1,2-dihydro-2,2-dimethyl-s-triazine with Va moles of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid); F. 212 0 C with decomposition after recrystallization from acetonitrile and water. 1) From 5.0 g of 4,6-diamino-l- (p-bromophenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine monohydrochloride and 3.38 g of 4,4'-methylene bis- (3-hydroxy-2-naphthoic acid) disodium salt monohydrate, the salt is obtained from 4,6-diamino-1 - (p-bromophenyl) -1,2-dihydro-2,2-dimethyl-s-triazine with Va mol 4,4'-methylenebis (3-hydroxy-2-naphthoic acid; chartreuse-colored crystals; mp 230 to 235 ° C.
m) Aus 4,0 g 4,6-Diamino-l,2-dihydro-l-(p-methoxyphenyl) - 2,2 - dimethyl - s - triazin - monohydrochlorid und 3,17 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatrium-monohydrat erhält man das Salz aus 4,6-Diamino-1,2-dihydro-1 -(p-methoxyphenyl)-2,2-dimethyl-s-triazin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); schwachgelbe Kristalle; F. 264 bis 267°C nach einer Umkristallisation aus Dimethylsulfoxyd und Wasser.m) From 4.0 g of 4,6-diamino-1,2-dihydro-1- (p-methoxyphenyl) -2,2-dimethyl-s-triazine-monohydrochloride and 3.17 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium monohydrate are obtained from the salt 4,6-diamino-1,2-dihydro-1 - (p-methoxyphenyl) -2,2-dimethyl-s-triazine with Va moles of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid); pale yellow crystals; F. 264 to 267 ° C after recrystallization from dimethyl sulfoxide and water.
n) Aus 1,97 g 4,6-Diamino-l-(m-chlorphenyl)-l,2-dihydro-2-propyl-s-triazin-monohydrochlorid und 1,46 g 4,4' - Methylen - bis - (3 - hydroxy - 2 - naphthoesäure) -dinatriumsalz-monohydrat erhält man das Salz aus 4,6-Diamino-l-(m-chlorphenyl)-l,2-dihydro-2-propyls-triazin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. 175° C unter Zersetzung nach einer Umkristallisation aus Acetonitril und Wasser oder Methanol und Wasser.n) From 1.97 g of 4,6-diamino-1- (m-chlorophenyl) -l, 2-dihydro-2-propyl-s-triazine monohydrochloride and 1.46 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate the salt is obtained from 4,6-diamino-1- (m-chlorophenyl) -l, 2-dihydro-2-propyls-triazine with Va moles of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid); F. 175 ° C with decomposition after a recrystallization from acetonitrile and water or methanol and water.
o) Aus 9,0 g 4,6-Diamino-l,2-dihydro-2,2-dimethyl-1-p-tolyl-s-triazin-monohydrochlorid und 7,55 g 4,4' - Methylen - bis - (3 - hydroxy - 2 - naphthoesäure) -dinatriumsalz-monohydrat erhält man das Salz auso) From 9.0 g of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-p-tolyl-s-triazine monohydrochloride and 7.55 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate you get the salt from
4545
droxy-2-naphthoesäure); F. unbestimmt, beginnend 50 4,6-Diamino-l^-dihydro^^-dimethyl-l-p-tolyl-s-tribei 19O0C nach einer Umkristallisation aus Methanol azin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naph- und Wasser. thoesäure); F. unbestimmt, beginnend bei 2000C nachhydroxy-2-naphthoic acid); F. undetermined, starting 50 4,6-diamino-l ^ -dihydro ^^ - dimethyl-lp-tolyl-s-tribei 19O 0 C after recrystallization from methanol azine with Va mol 4,4'-methylene-bis- ( 3-hydroxy-2-naph- and water, thoic acid); F. indefinite, starting at 200 0 C after
h) Aus 15,0 g4,6-Diamino-l,2-dihydro-2,2-dimethyl- einer Umkristallisation aus Methanol und Wasser.
l-(m-methylthiophenyl)-s-triazin-monohydrochlorid p) Aus 10,42 g 4,6-Diamino-l,2-dihydro-2,2-dime-h) From 15.0 g of 4,6-diamino-1,2-dihydro-2,2-dimethyl recrystallization from methanol and water.
l- (m-methylthiophenyl) -s-triazine-monohydrochloride p) From 10.42 g 4,6-diamino-1,2-dihydro-2,2-dim-
5555
und 11,3g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz aus 4,6-Diamino-l ,2-dihydro-2,2-dimethyl-l-(m-methylthiophenyl)-s-triazin mit Va Mol 4,4'-Methylenbis-(3-hydroxy-2-naphthoesäure); F. 191 bis 193°C nach einer Umkristallisation aus Acetonitril und Wasser.and 11.3 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate the salt is obtained from 4,6-diamino-1,2-dihydro-2,2-dimethyl-1- (m-methylthiophenyl) -s-triazine with Va moles of 4,4'-methylenebis (3-hydroxy-2-naphthoic acid); F. 191 to 193 ° C after recrystallization from acetonitrile and water.
i) Aus 13,6 g 4,6-Diamino-l,2-dihydro-2,2-dimethyl-1 - (α,α,α,4 - tetrafluor - m - tolyl) - s - triazin - monohydrochlorid und 9,0 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz von 4,6-Diamino-l,2-dihydro-2,2-dimethyl-l-(a,a, Ä,4-tetrafluor-m-tolyl)-s-triazin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. 180 bis thyl -1 - (p - methylthiophenyl) - s - triazin - monohydro chlorid und 7,65 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure) - dinatriumsalz - monohydrat erhält man das Salz aus 4,6-Diamino-l,2-dihydro-2,2-dimethyl-l-(p-methylthiophenyl)-s-triazin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. 234 bis 236,5° C nach einer Digerierung mit Acetonitril und Wasser.i) From 13.6 g of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1 - (α, α, α, 4 - tetrafluoro - m - tolyl) - s - triazine - monohydrochloride and 9.0 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate the salt of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1- (a, a, Ä, 4-tetrafluoro-m-tolyl) -s-triazine with Va mol of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid); F. 180 bis ethyl -1 - (p - methylthiophenyl) - s - triazine - monohydrochloride and 7.65 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate is obtained the salt of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1- (p-methylthiophenyl) -s-triazine with Va moles of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid); F. 234 to 236.5 ° C after digestion with acetonitrile and Water.
q) Aus 3,54 g 4,6-Diamino-1,2-dihydro-2,2-dimethyl-l-Ca^Ä-trifluor-p-tolyl-s-triazin-monohydro- chlorid und 2,47 g 4,4'-Methylen-bis-(3-hydroxy- - naphthoesäure) - dinatriumsalz - monohydrat erhält man das Salz von 4,6-Diamino-l,2-dihydro-2,2-dimethyl-l-(a,a,«-trifluor-p-tolyl)-s-triazin mit Va Molq) From 3.54 g of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-Ca ^ Ä-trifluoro-p-tolyl-s-triazine-monohydro- chloride and 2.47 g of 4,4'-methylene-bis (3-hydroxy- - naphthoic acid) - disodium salt - monohydrate the salt of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1- (a, a, «- trifluoro-p-tolyl) -s-triazine with Va Mol
4,4' - Methylen - bis - (3 - hydroxy - 2 - naphthoesäure); F. 2110C nach einer Umkristallisation aus Acetonitril und Wasser.4,4 '- methylene - bis - (3 - hydroxy - 2 - naphthoic acid); F. 211 0 C after recrystallization from acetonitrile and water.
r) Aus 10,49 g 4,6-Diamino-l-(3,4-dichlorphenyl)-1 ^-dihydro^-methyl-s-triazin-monohydrochlorid und 7,65 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz von 4,6-Diamino-1 -(3,4-dichlorphenyl)-1,2-dihydro-2-methyl-s-triazin mit V2 Mol 4,4'-Methylen-bis-(3-hydroxy-r) From 10.49 g of 4,6-diamino-1- (3,4-dichlorophenyl) -1 ^ -dihydro ^ -methyl-s-triazine-monohydrochloride and 7.65 g of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid) disodium salt monohydrate is obtained the salt of 4,6-diamino-1 - (3,4-dichlorophenyl) -1,2-dihydro-2-methyl-s-triazine with 2 V Moles of 4,4'-methylene-bis- (3-hydroxy-
droxy-2-naphthoesäure); F. unbestimmt, beginnend bei 2000C.hydroxy-2-naphthoic acid); F. indefinite, starting at 200 0 C.
z) Aus 4,12 g 4,6-Diamino-l-(3,5-dibromphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid 5 und 2,25 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat erhält man das Salz aus 4,6-Diamino-1 -(3,5-dibromphenyl)-1,2-dihydro-2,2-dimethyl-s-triazin mit Va Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. 210°C unter Zer-2-naphthoesäure); schwachgelbe Kristalle aus Aceto- io setzung.z) From 4.12 g of 4,6-diamino-1- (3,5-dibromophenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine monohydrochloride 5 and 2.25 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate the salt is obtained from 4,6-diamino-1 - (3,5-dibromophenyl) -1,2-dihydro-2,2-dimethyl-s-triazine with Va moles of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid); Mp 210 ° C under cerium-2-naphthoic acid); pale yellow crystals from acetoion.
nitrü und Wasser. aa) Aus 1,97 g 4,6-Diamino-l-(*3,«3,a3,«6,a5,*5-nitrate and water. aa) From 1.97 g 4,6-diamino-1 - (* 3 , « 3 , a 3 ,« 6 , a 5 , * 5 -
s) Aus 3,80 g 4,6-Diamino-l-(3-chlor-p-tolyl)-l,2-di- hexafluor-3,5-xylyl)-1,2-dihydro-2,2-dimethyl-s-trihydro^^-dimethyl-s-triazin-monohydrochlorid und azin-monohydrochlorid und 1,14 g 4,4'-Methylen-bis-2,75 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)- (3 - hydroxy - 2 - naphthoesäure) - dinatriumsalz - mono dinatriumsalz-monohydrat erhält man das Salz von 15 hydrat erhält man das Salz aus 4,6-Diamino-l-(a3,a3, 4,6-Diamino-l-(3-chlor-p-tolyl)-l,2-dihydro-2,2-dime- «s,a5,«6,3(5-hexafluor-3,5-xylyl)-l,2-dihydro-2,2-dimethyl-s-triazin mit V2M0I von 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. 225 0C unter Zersetzung nach einer Umkristallisation aus Dimethylsulfoxyd und Wasser.s) From 3.80 g of 4,6-diamino-1- (3-chloro-p-tolyl) -l, 2-di-hexafluoro-3,5-xylyl) -1,2-dihydro-2,2- dimethyl-s-trihydro ^^ - dimethyl-s-triazine-monohydrochloride and azine-monohydrochloride and 1.14 g of 4,4'-methylene-bis-2.75 g of 4,4'-methylene-bis- (3-hydroxy -2-naphthoic acid) - (3 - hydroxy - 2 - naphthoic acid) - disodium salt - monodisodium salt monohydrate if the salt of 15 hydrate is obtained, the salt is obtained from 4,6-diamino-1- (a 3 , a 3 , 4 , 6-diamino-1- (3-chloro-p-tolyl) -l, 2-dihydro-2,2-dime- « s , a 5 ,« 6 , 3 ( 5- hexafluoro-3,5-xylyl) -l, 2-dihydro-2,2-dimethyl-s-triazine with V2M0I of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid); F. 225 0 C with decomposition after recrystallization from dimethylsulfoxide and water.
t) Aus 10,6 g 4,6-Diamino-l-(p-chlorphenyl)-l,2-dihydro-2-methyl-s-triazin-monohydrochlorid und 8,68 g 4,4' - Methylen - bis - (3 - hydroxy - 2 - naphthoesäure) - di -t) From 10.6 g of 4,6-diamino-1- (p-chlorophenyl) -l, 2-dihydro-2-methyl-s-triazine monohydrochloride and 8.68 g 4,4 '- methylene - bis - (3 - hydroxy - 2 - naphthoic acid) - di -
thyl-s-triazin mit V2 Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. unbestimmt, beginnend bei 195°C.ethyl-s-triazine with V 2 moles of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid); F. indeterminate, starting at 195 ° C.
natriumsalz-monohydrat erhält man das Salz aussodium salt monohydrate is obtained from the salt
300 ecm heißem Methanol. Das Gemisch wird durch Destillation eingeengt und gekühlt. Das gelbe kristalline Produkt wird abgekühlt, mit Aceton gewaschen300 ecm of hot methanol. The mixture is concentrated by distillation and cooled. The yellow crystalline The product is cooled and washed with acetone
hydro-2,2-dimethyl-l-(3,4-xylyl)-s-triazin mit V2 Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. 228 bis 232° C nach Umkristallisation aus Methanol undhydro-2,2-dimethyl-1- (3,4-xylyl) -s-triazine with V2 mol 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid); F. 228 to 232 ° C after recrystallization from methanol and
den Arbeitsweise an Stelle des Dinatriumsalzes verwendet werden. In gleicher Weise können andere lösliche Salze von 4,6-Diamino-l,2-dihydro-2,2-di~the procedure can be used in place of the disodium salt. In the same way, other soluble Salts of 4,6-diamino-1,2-dihydro-2,2-di ~
Eine Lösung von 19,7 g 4,6-Diamino-1,2-dihydro-2,2-dimethyl-l-(3,4-xylyl)-s-triazin-monohydrochlorid
in 500 ecm heißem Methanol gießt man unter Rühren 4,6-Diamino-l-(p-chlorphenyl)-l,2-dihydro-2-methyl- 25 in eine Lösung von 15,7 g 4,4'-Methylen-bis-(3-hys-triazin
mit Va Mol 4,4'-Methylen-bis-(3-hydroxy- droxy-2-naphthoesäure)-dinatriumsalz-monohydrat in
2-naphthoesäure); F. unbestimmt, beginnend bei 188 0C
nach einer Umkristallisation aus Methanol und Wasser,
u) Aus 14,4 g 4,6-Diamino-l-(p-chlorphenyl)-l,2-dihydro-2-äthyl-s-triazin-monohydrochlorid
und 11,25 g 30 und im Vakuum 18 Stunden bei 60°C getrocknet. 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-di- Dieses Produkt ist das Salz von 4,6-Diamino-l,2-dinatriumsalz-monohydrat
erhält man das Salz aus
4,6-Diamino-1 -(p-chlorphenyl) -l,2-dihydro-2- äthyls-triazin
mit V2 Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure);
F. 2080C unter Zersetzung nach 35 Wasser. Das Dikaliumsalz von 4,4'-Methylen-biseiner
Umkristallisation aus Methanol und Wasser. (3-hydroxy-2-naphthoesäure) kann bei der vorstehen-A solution of 19.7 g of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1- (3,4-xylyl) -s-triazine monohydrochloride in 500 ecm of hot methanol is poured with stirring 4 , 6-diamino-1- (p-chlorophenyl) -l, 2-dihydro-2-methyl-25 in a solution of 15.7 g of 4,4'-methylene-bis- (3-hys-triazine with Va Mol 4,4'-methylene-bis (3-hydroxydroxy-2-naphthoic acid) disodium salt monohydrate in 2-naphthoic acid); F. indeterminate, starting at 188 ° C
after recrystallization from methanol and water,
u) From 14.4 g of 4,6-diamino-1- (p-chlorophenyl) -l, 2-dihydro-2-ethyl-s-triazine monohydrochloride and 11.25 g of 30 and in vacuo at 60 ° for 18 hours C dried. 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid) -di This product is the salt of 4,6-diamino-1,2-disodium salt monohydrate is obtained from the salt
4,6-diamino-1 - (p-chlorophenyl) -l, 2-dihydro-2-ethyls-triazine with V 2 moles of 4,4'-methylenebis (3-hydroxy-2-naphthoic acid); F. 208 0 C with decomposition after 35 water. The dipotassium salt of 4,4'-methylene-bis, recrystallized from methanol and water. (3-hydroxy-2-naphthoic acid) can be used in the
v) Aus 2,12 g ^o-Diamino-l^-dihydro-^-dimethyll-(Ä,«,*-trifluor-m-tolyl)-s-triazin-monohydrochlorid
und 1,48 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat
erhält man das Salz 40 methyl-1-(3,4-xylyl)-s-triazin, wie das Sulfat oder das
von 4,6-Diamino-1,2-dihydro-2,2-dimethyl-1 -(<x,x, Acetat, an Stelle des Hydrochlorids verwendet werden.
Ä-trifluor-m-tolyl)-s-triazin mit 1J2 Mol 4,4'-Methylen- . . .v) From 2.12 g ^ o-diamino-l ^ -dihydro- ^ - dimethyll- (Ä, «, * - trifluoro-m-tolyl) -s-triazine-monohydrochloride
and 1.48 g of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid) disodium salt monohydrate, the salt 40 methyl-1- (3,4-xylyl) -s-triazine is obtained, like that Sulphate or that of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1 - (<x, x, acetate, can be used in place of the hydrochloride. Ä-trifluoro-m-tolyl) -s- triazine with 1 J 2 moles of 4,4'-methylene. . .
bis-(3-hydroxy-2-naphthoesäure); F. 168 bis 1700C Beispiel jbis (3-hydroxy-2-naphthoic acid); F. 168 to 170 0 C example j
nach einer Umkristallisation aus Äthylenglykolmono- Eine Lösung von 0,576 g 4,6-Diamino-l-(p-chIor-after recrystallization from ethylene glycol mono- A solution of 0.576 g of 4,6-diamino-l- (p-chloro-
methyläther und Wasser. 45 phenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-monohydro-methyl ether and water. 45 phenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine-monohydro-
w) Aus 38,0 g4,6-Diamino-l-(p-brorn-a,a,a-trifluor- chlorid in 5 ecm heißem Wasser gibt man zu einerw) From 38.0 g of 4,6-diamino-l- (p-bromine-a, a, a-trifluorochloride in 5 ecm of hot water is added to a
Lösung von 0,388 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure) in 5 ecm N,N-Dimethylacetamid. 2 ecm Ι,Οη-Natriumlauge werden schnell hinzugeman das Salz aus 4,6-Diamino-l-(p-brom-«,a,a-tri- 50 geben, und das Gemisch wird erhitzt, bis sich eine fluor-m-tolyl)-l,2-dihydro-2,2-dimethyl-s-triazin mit leuchtendgelbe Kristallmasse gebildet hat. Das Ge-V2 Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoe- misch wird abgekühlt, und das Produkt wird dann säure); F. 1890C unter Zersetzung nach einer Um- abfiltriert und getrocknet. Diese Verbindung ist das kristallisation aus Acetonitril und Wasser. Salz aus 4,6-Diamino-1-(p-chlorphenyl)-1,2-dihydro-Solution of 0.388 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) in 5 ecm of N, N-dimethylacetamide. 2 ecm Ι, Οη-sodium hydroxide solution are quickly added man the salt of 4,6-diamino-l- (p-brom- «, a, a-tri- 50, and the mixture is heated until a fluorine-m- tolyl) -l, 2-dihydro-2,2-dimethyl-s-triazine with a bright yellow crystal mass. The Ge-V 2 moles of 4,4'-methylene-bis- (3-hydroxy-2-naphthoe- mix is cooled and the product then becomes acid); F. 189 0 C with decomposition after a re-filtered off and dried. This compound is the crystallization from acetonitrile and water. Salt of 4,6-diamino-1- (p-chlorophenyl) -1,2-dihydro-
x) Aus 5,17 g 4,6-Diamino-l-(3,5-dichlorphenyl)- 55 2,2-dimethyl-s-triazin mit V2M0I 4,4'-Methylen-bisl^-dihydro^^-dimethyl-s-triazin-monohydrochlorid
(3-hydroxy-2-naphthoesäure); F. 231 bis 2340C nach und 3,6 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat
erhält man das Salz
von 4,6-Diamino-1 -(3,5-dichlorphenyl)-1,2-dihydro-2,2-dimethyl-s-triazin
mit V2 Mol 4,4'-Methylen-bis~ 60
(3-hydroxy-2-naphthoesäure); F. 221° C nach einer
Umkristallisation aus Methanol und Wasser.x) From 5.17 g of 4,6-diamino-1- (3,5-dichlorophenyl) - 55 2,2-dimethyl-s-triazine with V2M0I 4,4'-methylene-bisl ^ -dihydro ^^ - dimethyl -s-triazine monohydrochloride (3-hydroxy-2-naphthoic acid); The salt is obtained from 231 to 234 ° C. and 3.6 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate
of 4,6-diamino-1 - (3,5-dichlorophenyl) -1,2-dihydro-2,2-dimethyl-s-triazine with V2 moles of 4,4'-methylene-to ~ 60
(3-hydroxy-2-naphthoic acid); F. 221 ° C after a
Recrystallization from methanol and water.
y)Aus3,22g4,6-Diamino-l-(5-brom-m-tolyl)-l,2-dihydro - 2,2 - dimethyl-s - triazin - monohydrochlorid undy) From 3.22g4,6-diamino-1- (5-bromo-m-tolyl) -l, 2-dihydro - 2,2 - dimethyl-s - triazine - monohydrochloride and
2,08 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)- 65 l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid dinatriumsalz-monohydrat erhält man das Salz aus in 100 ecm Wasser mit 10 ecm 1,0 η-Salzsäure. Das sich 4,6-Diamino-l-(5-brom-m-tolyl)-l,2-dihydro-2,2-di- bildende unlösliche Salz wird abfiltriert und getrocknet, methyl-s-triazin mit Va M°l 4,4'-Methylen-bis-(3-hy- Es ist das Salz aus 4,6-Diamino-l-(p-chlorphenyl)-The salt is obtained from in 100 ecm of water with 10 ecm of 1.0 η hydrochloric acid. The 4,6-diamino-1- (5-bromo-m-tolyl) -l, 2-dihydro-2,2-di- forming insoluble salt is filtered off and dried, methyl-s-triazine with Va M ° l 4,4'-methylene-bis- (3-hy- It is the salt of 4,6-diamino-l- (p-chlorophenyl) -
m-tolyl)-1 ^-dihydro^^-dimethyl-s-triazin-rnonohydrochlorid und 21,4g 4,4'-Methylen-bis-(3-hydroxy-2 - naphthoesäure) - dinatriumsalz-monohydrat erhältm-tolyl) -1 ^ -dihydro ^^ - dimethyl-s-triazine-monohydrochloride and 21.4 g of 4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid) disodium salt monohydrate
einer Umkristallisation
Wasser.a recrystallization
Water.
aus Dimethylsulfoxyd undfrom dimethyl sulfoxide and
Eine Lösung von 4,50 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat in 100 ecm Wasser gießt man unter kräftigem Rühren in eine Lösung von 2,88 g 4,6-Diamino-l-(p-chlorphenyl)-A solution of 4.50 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate in 100 ecm of water is poured into a solution of 2.88 g of 4,6-diamino-1- (p-chlorophenyl) - with vigorous stirring
l,2-dihydro-2,2-dimethyl-s-triazin mit 1 Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure); F. unbestimmt, beginnend bei 2250C. Die gleiche Verbindung erhält man durch Zugabe von 10 ecm von 1,On-SaIzsäure zu einer Lösung von 4,50 g 4,4'-Methylen-bis-(3 - hydroxy - 2 - naphthoesäure) - dinatriumsalz - mono hydrat in 50 ecm Wasser und anschließende Zugabe dieses Gemisches unter starkem Rühren in eine Lösung von 2,88 g4,6-Diamino-l-(p-chlorphenyl)-l,2-dihydro-2,2-dimethyl-s-triazin-monohydrochlorid in 100 ecm Wasser.1,2-dihydro-2,2-dimethyl-s-triazine with 1 mole of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid); F. indefinite, starting at 225 0 C. The same compound is obtained by adding 10 cc of 1, On-SaIzsäure to a solution of 4.50 g of 4,4'-methylene-bis- (3 - hydroxy - 2 - naphthoic acid) - disodium salt - monohydrate in 50 ecm of water and subsequent addition of this mixture with vigorous stirring in a solution of 2.88 g of 4,6-diamino-l- (p-chlorophenyl) -l, 2-dihydro-2,2- dimethyl-s-triazine monohydrochloride in 100 ecm of water.
Durch geeignete Auswahl der Reaktionsbedingungen können die vorstehenden Produkte in der gewünschten Kristallgröße erhalten werden. Wenn man eine Lösung von 32,6 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat in 400 ecm warmem Wasser in eine Lösung von 40,5 g 4,6-Diamino-l-(p - chlorphenyl) -1,2 - dihydro - 2,2 - dimethyl - s - triazin monohydrochlorid in 600 ecm heißem Methanol gießt, wird das sich abscheidende Produkt in Form von großen Kristallen erhalten. Wenn eine Lösung von 31,6 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat in 400 ecm Acetonitril—■ Wasser (3: 2) zugegeben wird zu einer Lösung von 40,5 g 4,6 - Diamino -1 - (ρ - chlorphenyl) -1,2 - dihydro 2,2-dimethyl-s-triazin-monohydrochlorid in 600 ecm Acetonitril—Wasser (3 : 2), wird das sich abscheidende Produkt in Form von kleinen gelben Nadeln gewonnen.By properly selecting the reaction conditions, the above products can be used in the desired Crystal size can be obtained. If you have a solution of 32.6 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate in 400 ecm warm water in a solution of 40.5 g 4,6-diamino-l- (p - chlorophenyl) -1,2 - dihydro - 2,2 - dimethyl - s - triazine monohydrochloride Poured into 600 ecm of hot methanol, the product that separates out is in the form of Obtain large crystals. When a solution of 31.6 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate in 400 ecm acetonitrile— ■ water (3: 2) is added to a solution of 40.5 g of 4,6 - diamino -1 - (ρ - chlorophenyl) -1,2 - dihydro 2,2-dimethyl-s-triazine monohydrochloride in 600 ecm acetonitrile water (3: 2), the separating Product obtained in the form of small yellow needles.
Eine Lösung von 5,85 g 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure)-dinatriumsalz-monohydrat in 50 ecm Wasser gießt man unter Rühren in eine Lösung von 10,0 g 4,6-Diamino-l-(p-benzyloxyphenyl)-l,2-dihydro - 2,2 - dimethyl - s - triazin - monohydrochlorid - di hydrat in 150 ecm warmem Wasser. Das sich abscheidende Produkt ist das Salz aus 4,6-Diaminol-(p-benzyloxyphenyl)-l,2-dihydro-2,2-dimethyl-s-tri- azin mit 1J2 Mol 4,4'-Methylen-bis-(3-hydroxy-2-naphthoesäure) und wird abfiltriert und getrocknet; F. 182 bis 1850C nach einer Umkristallisation aus Acetonitril und Wasser.A solution of 5.85 g of 4,4'-methylene-bis (3-hydroxy-2-naphthoic acid) disodium salt monohydrate in 50 ecm of water is poured into a solution of 10.0 g of 4,6-diamino with stirring -l- (p-benzyloxyphenyl) -l, 2-dihydro - 2,2 - dimethyl - s - triazine - monohydrochloride - dihydrate in 150 ecm warm water. The product which separates out is the salt of 4,6-diaminol- (p-benzyloxyphenyl) -l, 2-dihydro-2,2-dimethyl-s-triazine with 1 J 2 moles of 4,4'-methylene-bis - (3-hydroxy-2-naphthoic acid) and is filtered off and dried; F. 182 to 185 0 C after recrystallization from acetonitrile and water.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8390961A | 1961-01-23 | 1961-01-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1171439B true DE1171439B (en) | 1964-06-04 |
Family
ID=22181439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEP28646A Pending DE1171439B (en) | 1961-01-23 | 1962-01-22 | Process for the preparation of salts of 4, 6-diamino-1, 2-dihydro-2-lower-alkyl-1-aryl-s-triazines with 4, 4'-methylene-bis- (3-hydroxy-2- naphthoic acid) |
Country Status (7)
| Country | Link |
|---|---|
| BR (1) | BR6235803D0 (en) |
| CH (1) | CH397708A (en) |
| DE (1) | DE1171439B (en) |
| DK (1) | DK104411C (en) |
| ES (1) | ES273934A1 (en) |
| GB (1) | GB986811A (en) |
| SE (1) | SE301479B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU601145B2 (en) * | 1985-03-01 | 1990-09-06 | Duphar International Research B.V. | Benzoyl urea derivatives having anti-tumor activity |
| CN114591256B (en) * | 2022-02-15 | 2024-02-20 | 上海奥萝拉医药科技有限公司 | Directional synthesis method of dihydrotriazine |
-
1962
- 1962-01-17 SE SE476/62A patent/SE301479B/xx unknown
- 1962-01-22 DK DK29162AA patent/DK104411C/en active
- 1962-01-22 ES ES0273934A patent/ES273934A1/en not_active Expired
- 1962-01-22 BR BR135803/62A patent/BR6235803D0/en unknown
- 1962-01-22 CH CH74062A patent/CH397708A/en unknown
- 1962-01-22 GB GB2325/62A patent/GB986811A/en not_active Expired
- 1962-01-22 DE DEP28646A patent/DE1171439B/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| BR6235803D0 (en) | 1973-05-24 |
| CH397708A (en) | 1965-08-31 |
| ES273934A1 (en) | 1962-06-16 |
| GB986811A (en) | 1965-03-24 |
| DK104411C (en) | 1966-05-16 |
| SE301479B (en) | 1968-06-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1238476B (en) | Process for the preparation of lower alkyl esters of a 6,7-dialkoxy-4-hydroxy-3-quinolinecarboxylic acid which are suitable for combating parasitic infections in veterinary medicine | |
| EP0172515B1 (en) | Alpha-(o-chlorophenyl)-aminomethylene-beta-formylamino-propionitrile, process for its preparation and its use in the preparation of 2-methyl-4-amino-5-formylaminomethyl pyrimidine | |
| DE1118789B (en) | Process for the preparation of 1, 3, 5-triazine derivatives | |
| DE3121922C2 (en) | 2-Amino-4-nicotinoylamino-6-halophenyl-s-triazines, processes for their preparation and pharmaceutical compositions containing them | |
| DE1171439B (en) | Process for the preparation of salts of 4, 6-diamino-1, 2-dihydro-2-lower-alkyl-1-aryl-s-triazines with 4, 4'-methylene-bis- (3-hydroxy-2- naphthoic acid) | |
| DE1150991B (en) | Process for the preparation of 7-sulfamyl-3, 4-dihydro-1, 2, 4-benzothiadiazine-1, 1-dioxydes | |
| DE1197463B (en) | Process for the preparation of salts of 2, 4-diamino-5- (p-chlorophenyl) -6-aethyl-pyrimidine with 3, 3'-dioxy-4, 4'-methylene-dinaphthoic acid- (2) | |
| DE1965711B2 (en) | l ^ -Dihydro-133-triazine derivatives, processes for their preparation and medicaments containing them | |
| US3074947A (en) | Certificate of correction | |
| AT234710B (en) | Process for the preparation of new 4, 6-diamino-1, 2-dihydro-2- (lower alkyl) -1-aryl-s-triazine salts | |
| DE1695117C3 (en) | Process for the preparation of chloramino-s-triazines | |
| DE680661C (en) | Process for the preparation of cyclic amidines substituted in the amino groups | |
| DE2409195C3 (en) | Process for the preparation of imidazole-43-dicarboxamide | |
| DE896492C (en) | Process for the preparation of 2-haloarylamino-4-amino-1, 3, 5-triazine derivatives | |
| DE1670143C3 (en) | ||
| DD252374A1 (en) | PROCESS FOR THE PREPARATION OF 2-AMINO-4-ALKOXY-6-ALKYL-1,3,5-TRIAZINENE | |
| DE831697C (en) | Process for the preparation of new pyrimidylaminoquinoline derivatives | |
| DE1670550B2 (en) | SUBSTITUTED 2-AMINO-4-HYDRAZINO6-PIPERAZINO-S-TRIAZINE | |
| DE615184C (en) | Process for the preparation of amino compounds of the quinoline series | |
| DE1245973B (en) | Process for the preparation of amino-substituted l ^ -dihydro-i-hydroxy-lJ.S-triazines | |
| DE648062C (en) | Process for the production of barbituric acid coagulations | |
| DE1124504B (en) | Process for the preparation of 2-methyl-3- (2 ', 4'-dimethylphenyl) -4-oxo-3,4-dihydroquinazoline. | |
| DE1115260B (en) | Process for the preparation of purine derivatives | |
| DE1198817B (en) | Process for the preparation of cycloalkyloxyalkylguanidines | |
| DE735596C (en) | Process for the preparation of higher molecular weight 2,4-diamino-1,3,5-triazine derivatives |