TW200904811A - Use of 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester for preparing the tryptase inhibitor [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone - Google Patents

Use of 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester for preparing the tryptase inhibitor [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone Download PDF

Info

Publication number: TW200904811A
Authority: TW; Taiwan
Prior art keywords: methyl; thiophene; bromo; propoxy; carboxylic acid
Prior art date: 2007-03-29

Application number

TW097111154A

Other languages

English (en)

Chinese (zh)

Inventor

Ann Marie Gelormini

John J Shay

Adam W Sledeski

Original Assignee

Sanofi Aventis

Priority date (The priority date 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 date listed.)

2007-03-29

Filing date

2008-03-28

Publication date

2009-02-01

2008-03-28 Application filed by Sanofi Aventis filed Critical Sanofi Aventis

2009-02-01 Publication of TW200904811A publication Critical patent/TW200904811A/zh

Links

229940122598 Tryptase inhibitor Drugs 0.000 title description 2
239000002750 tryptase inhibitor Substances 0.000 title description 2
IOKNJMJJWUNVRG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-bromo-3-methyl-5-propoxythiophene-2-carboxylate Chemical compound BrC1=C(OCCC)SC(C(=O)ON2C(CCC2=O)=O)=C1C IOKNJMJJWUNVRG-UHFFFAOYSA-N 0.000 title 1
IFWLUOOAWLUBQN-UHFFFAOYSA-N [4-[5-(aminomethyl)-2-fluorophenyl]piperidin-1-yl]-(4-bromo-3-methyl-5-propoxythiophen-2-yl)methanone Chemical compound BrC1=C(OCCC)SC(C(=O)N2CCC(CC2)C=2C(=CC=C(CN)C=2)F)=C1C IFWLUOOAWLUBQN-UHFFFAOYSA-N 0.000 title 1
239000002904 solvent Substances 0.000 claims abstract description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 11
238000000034 method Methods 0.000 claims description 32
238000005859 coupling reaction Methods 0.000 claims description 17
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 6
238000010511 deprotection reaction Methods 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 4
150000003512 tertiary amines Chemical class 0.000 claims description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 1
239000004472 Lysine Substances 0.000 claims 1
238000005576 amination reaction Methods 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
-1 4-bromo-3-methyl-5-propoxy-thiophene-2-carboxylic acid compound Chemical class 0.000 abstract description 17
239000002585 base Substances 0.000 abstract description 15
230000015572 biosynthetic process Effects 0.000 abstract description 5
239000010949 copper Substances 0.000 abstract description 5
239000004215 Carbon black (E152) Substances 0.000 abstract description 4
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 abstract description 4
229910052783 alkali metal Inorganic materials 0.000 abstract description 4
239000003054 catalyst Substances 0.000 abstract description 4
229910052802 copper Inorganic materials 0.000 abstract description 4
229930195733 hydrocarbon Natural products 0.000 abstract description 4
150000002430 hydrocarbons Chemical class 0.000 abstract description 4
238000006887 Ullmann reaction Methods 0.000 abstract description 3
150000002576 ketones Chemical class 0.000 abstract description 3
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 abstract description 3
238000003786 synthesis reaction Methods 0.000 abstract description 2
XAOJMTRGEZJSQN-UHFFFAOYSA-N 3-methyl-5-propoxythiophene-2-carboxylic acid Chemical compound CCCOC1=CC(C)=C(C(O)=O)S1 XAOJMTRGEZJSQN-UHFFFAOYSA-N 0.000 abstract 3
BSQKBHXYEKVKMN-UHFFFAOYSA-N 3-methylthiophene-2-carbaldehyde Chemical compound CC=1C=CSC=1C=O BSQKBHXYEKVKMN-UHFFFAOYSA-N 0.000 abstract 3
UTFHYWYDDMHEIL-UHFFFAOYSA-N 5-iodo-3-methylthiophene-2-carbaldehyde Chemical compound CC=1C=C(I)SC=1C=O UTFHYWYDDMHEIL-UHFFFAOYSA-N 0.000 abstract 2
NBLCMBNKWZHYLB-UHFFFAOYSA-N 5-iodo-3-methylthiophene-2-carboxylic acid Chemical compound CC=1C=C(I)SC=1C(O)=O NBLCMBNKWZHYLB-UHFFFAOYSA-N 0.000 abstract 2
VWFVJVPPXXCWAW-UHFFFAOYSA-N 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid Chemical compound CCCOC=1SC(C(O)=O)=C(C)C=1Br VWFVJVPPXXCWAW-UHFFFAOYSA-N 0.000 abstract 1
230000003301 hydrolyzing effect Effects 0.000 abstract 1
230000002083 iodinating effect Effects 0.000 abstract 1
230000001590 oxidative effect Effects 0.000 abstract 1
239000000203 mixture Substances 0.000 description 23
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
239000000243 solution Substances 0.000 description 16
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
239000007787 solid Substances 0.000 description 9
125000000217 alkyl group Chemical group 0.000 description 7
230000008569 process Effects 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000012267 brine Substances 0.000 description 6
230000008878 coupling Effects 0.000 description 6
238000010168 coupling process Methods 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
239000007789 gas Substances 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
238000005406 washing Methods 0.000 description 5
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
150000001875 compounds Chemical class 0.000 description 4
239000004744 fabric Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
229910052700 potassium Inorganic materials 0.000 description 4
239000011591 potassium Substances 0.000 description 4
239000011734 sodium Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
101150041968 CDC13 gene Proteins 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
102000001400 Tryptase Human genes 0.000 description 3
108060005989 Tryptase Proteins 0.000 description 3
239000002253 acid Substances 0.000 description 3
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
229940126142 compound 16 Drugs 0.000 description 3
230000032050 esterification Effects 0.000 description 3
238000005886 esterification reaction Methods 0.000 description 3
235000019439 ethyl acetate Nutrition 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
239000011630 iodine Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000002390 rotary evaporation Methods 0.000 description 3
239000002002 slurry Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
LMUFKHXTMZDSLV-UHFFFAOYSA-N CCCOC1=C(C(=C(S1)C(=O)O)C2=CC3=CC=CC=C3N2)Br Chemical compound CCCOC1=C(C(=C(S1)C(=O)O)C2=CC3=CC=CC=C3N2)Br LMUFKHXTMZDSLV-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical class N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
230000031709 bromination Effects 0.000 description 2
238000005893 bromination reaction Methods 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
239000006184 cosolvent Substances 0.000 description 2
239000007822 coupling agent Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
229920001971 elastomer Polymers 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
239000012336 iodinating agent Substances 0.000 description 2
230000026045 iodination Effects 0.000 description 2
238000006192 iodination reaction Methods 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
239000001294 propane Substances 0.000 description 2
239000002994 raw material Substances 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
CVOGMKGEVNGRSK-UHFFFAOYSA-N 1,2-diiodoethene Chemical group IC=CI CVOGMKGEVNGRSK-UHFFFAOYSA-N 0.000 description 1
VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 1
KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
JQJBQVRTSMGDJX-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxy]decane Chemical compound CCCCCCCCCCOC(C)(C)C JQJBQVRTSMGDJX-UHFFFAOYSA-N 0.000 description 1
IANXAXNUNBAWBA-UHFFFAOYSA-N 2,2,3-trimethylundecane Chemical compound CCCCCCCCC(C)C(C)(C)C IANXAXNUNBAWBA-UHFFFAOYSA-N 0.000 description 1
ZNOVTXRBGFNYRX-UHFFFAOYSA-N 2-[[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-UHFFFAOYSA-N 0.000 description 1
XSJVWZAETSBXKU-UHFFFAOYSA-N 2-ethoxypropane Chemical compound CCOC(C)C XSJVWZAETSBXKU-UHFFFAOYSA-N 0.000 description 1
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
PQVSXGVVNMUVKK-UHFFFAOYSA-N C1=C(SC=C1S)I Chemical compound C1=C(SC=C1S)I PQVSXGVVNMUVKK-UHFFFAOYSA-N 0.000 description 1
GQDAWJCBZUVAPH-UHFFFAOYSA-N CCCOC1=C(C(=C(S1)C(=O)ON2OCCO2)C3=CC4=CC=CC=C4N3)Br Chemical compound CCCOC1=C(C(=C(S1)C(=O)ON2OCCO2)C3=CC4=CC=CC=C4N3)Br GQDAWJCBZUVAPH-UHFFFAOYSA-N 0.000 description 1
HXMXKTLCQSMDSQ-UHFFFAOYSA-N CCCOC1=CC(=C(S1)C(=O)O)S Chemical compound CCCOC1=CC(=C(S1)C(=O)O)S HXMXKTLCQSMDSQ-UHFFFAOYSA-N 0.000 description 1
OECCERLPNOREAF-UHFFFAOYSA-N Cl.FC(C(=O)NNNC1=CC(=C(C=C1)F)C1CCNCC1)(F)F Chemical compound Cl.FC(C(=O)NNNC1=CC(=C(C=C1)F)C1CCNCC1)(F)F OECCERLPNOREAF-UHFFFAOYSA-N 0.000 description 1
229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
108090000189 Neuropeptides Proteins 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
229910004298 SiO 2 Inorganic materials 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
125000002015 acyclic group Chemical group 0.000 description 1
238000007605 air drying Methods 0.000 description 1
125000002723 alicyclic group Chemical group 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
210000000621 bronchi Anatomy 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003245 coal Substances 0.000 description 1
229940125758 compound 15 Drugs 0.000 description 1
PDZKZMQQDCHTNF-UHFFFAOYSA-M copper(1+);thiocyanate Chemical compound [Cu+].[S-]C#N PDZKZMQQDCHTNF-UHFFFAOYSA-M 0.000 description 1
BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
PPCXFTKZPBHXIW-UHFFFAOYSA-N ethyl ethanesulfonate Chemical compound CCOS(=O)(=O)CC PPCXFTKZPBHXIW-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
239000001307 helium Substances 0.000 description 1
229910052734 helium Inorganic materials 0.000 description 1
SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
239000001272 nitrous oxide Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Inorganic materials [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000002689 soil Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000010959 steel Substances 0.000 description 1
125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
MUQNAPSBHXFMHT-UHFFFAOYSA-N tert-butylhydrazine Chemical compound CC(C)(C)NN MUQNAPSBHXFMHT-UHFFFAOYSA-N 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
230000007704 transition Effects 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Plural Heterocyclic Compounds (AREA)

TW097111154A 2007-03-29 2008-03-28 Use of 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester for preparing the tryptase inhibitor [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone TW200904811A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US90884407P	2007-03-29	2007-03-29

Publications (1)

Publication Number	Publication Date
TW200904811A true TW200904811A (en)	2009-02-01

Family

ID=39535396

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
TW097111154A TW200904811A (en)	2007-03-29	2008-03-28	Use of 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester for preparing the tryptase inhibitor [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone

Country Status (3)

Country	Link
AR (1)	AR065858A1 (es)
TW (1)	TW200904811A (es)
WO (1)	WO2008121666A1 (es)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HRP20151338T1 (hr) *	2008-08-22	2016-01-15	Sanofi	[4-(5-aminometil-2-fluoro-fenil)-piperidin-1-il]-[7-fluoro-1-(2-metoksi-etil)-4trifluorometoksi-1h-indol-3-il]metanon kao inhibitor triptaze mastocita
GB0905955D0 (en)	2009-04-06	2009-05-20	Respivert Ltd	Novel compounds
JP5787977B2 (ja)	2010-04-08	2015-09-30	レスピバート・リミテツド	Ｐ３８ｍａｐキナーゼ阻害剤
EP2582700B1 (en)	2010-06-17	2016-11-02	Respivert Limited	Respiratory formulations containing p38 mapk inhibitors

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DOP2005000039A (es) *	2004-03-26	2005-10-31	Aventis Pharma Inc	Hidrocloruro de [4-(5-aminometil-2-fluoro-fenil)- piperidin-1-il]-(4-bomo-3-metil-5-propoxi-tiofen-2-il)-metanona como un inhibidor de la triptasa de mastocitos

2008
- 2008-03-27 AR ARP080101260A patent/AR065858A1/es not_active Application Discontinuation
- 2008-03-27 WO PCT/US2008/058341 patent/WO2008121666A1/en not_active Ceased
- 2008-03-28 TW TW097111154A patent/TW200904811A/zh unknown

Also Published As

Publication number	Publication date
WO2008121666A1 (en)	2008-10-09
AR065858A1 (es)	2009-07-08

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