BRPI0622030A2 - Derivados de purina 7-substituída, para imunossupressão - Google Patents

Info

Publication number

BRPI0622030A2

BRPI0622030A2 BRPI0622030-4A BRPI0622030A BRPI0622030A2 BR PI0622030 A2 BRPI0622030 A2 BR PI0622030A2 BR PI0622030 A BRPI0622030 A BR PI0622030A BR PI0622030 A2 BRPI0622030 A2 BR PI0622030A2

Authority

BR

Brazil

Prior art keywords

substituted

alkyl

purine derivatives

formula

heterocyclyl

Prior art date

2006-11-16

Links

• Espacenet
• Global Dossier
• Discuss

• -1 7-SUBSTITUTED PURINE Chemical class 0.000 title claims description 127
• 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title claims description 43
• 206010062016 Immunosuppression Diseases 0.000 title claims description 5
• 230000001506 immunosuppresive effect Effects 0.000 title claims description 5
• 150000001875 compounds Chemical class 0.000 claims description 175
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 134
• 239000000203 mixture Substances 0.000 claims description 134
• 238000000034 method Methods 0.000 claims description 77
• 125000000623 heterocyclic group Chemical group 0.000 claims description 58
• 125000000217 alkyl group Chemical group 0.000 claims description 49
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 42
• 229910052739 hydrogen Inorganic materials 0.000 claims description 42
• 239000001257 hydrogen Substances 0.000 claims description 41
• 229910052736 halogen Inorganic materials 0.000 claims description 38
• 125000001072 heteroaryl group Chemical group 0.000 claims description 37
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
• 150000002367 halogens Chemical class 0.000 claims description 36
• 229910052757 nitrogen Inorganic materials 0.000 claims description 36
• 125000001424 substituent group Chemical group 0.000 claims description 34
• 125000003545 alkoxy group Chemical group 0.000 claims description 32
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 23
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 21
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 21
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 20
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 20
• 229910052760 oxygen Inorganic materials 0.000 claims description 20
• 235000019000 fluorine Nutrition 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• 210000000056 organ Anatomy 0.000 claims description 18
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 17
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 17
• HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 16
• 125000004442 acylamino group Chemical group 0.000 claims description 16
• 229910052799 carbon Inorganic materials 0.000 claims description 16
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 16
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 15
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 14
• 208000035475 disorder Diseases 0.000 claims description 14
• 208000023275 Autoimmune disease Diseases 0.000 claims description 13
• 125000003118 aryl group Chemical group 0.000 claims description 13
• 239000011737 fluorine Substances 0.000 claims description 13
• 229910052731 fluorine Inorganic materials 0.000 claims description 13
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
• 150000002431 hydrogen Chemical class 0.000 claims description 12
• UFZNZKGKBWOSJG-UHFFFAOYSA-N purin-2-one Chemical compound O=C1N=CC2=NC=NC2=N1 UFZNZKGKBWOSJG-UHFFFAOYSA-N 0.000 claims description 12
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
• 125000003282 alkyl amino group Chemical group 0.000 claims description 11
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 10
• 210000003630 histaminocyte Anatomy 0.000 claims description 10
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 10
• 230000001404 mediated effect Effects 0.000 claims description 10
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 claims description 9
• 125000000033 alkoxyamino group Chemical group 0.000 claims description 9
• VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 claims description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 8
• 125000001769 aryl amino group Chemical group 0.000 claims description 8
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
• 125000001188 haloalkyl group Chemical group 0.000 claims description 8
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 8
• WGSMVIHKBMAWRN-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1-benzofuran Chemical compound C1C=CC=C2OCCC21 WGSMVIHKBMAWRN-UHFFFAOYSA-N 0.000 claims description 7
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 7
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
• 125000005843 halogen group Chemical group 0.000 claims description 7
• 208000027866 inflammatory disease Diseases 0.000 claims description 7
• UHHKSVZZTYJVEG-UHFFFAOYSA-N oxepane Chemical group C1CCCOCC1 UHHKSVZZTYJVEG-UHFFFAOYSA-N 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 150000003212 purines Chemical class 0.000 claims description 7
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 7
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
• 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 6
• YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• HORKYAIEVBUXGM-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoxaline Chemical compound C1=CC=C2NCCNC2=C1 HORKYAIEVBUXGM-UHFFFAOYSA-N 0.000 claims description 5
• 206010025323 Lymphomas Diseases 0.000 claims description 5
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
• QPJDMGCKMHUXFD-UHFFFAOYSA-N cyanogen chloride Chemical compound ClC#N QPJDMGCKMHUXFD-UHFFFAOYSA-N 0.000 claims description 5
• 230000005764 inhibitory process Effects 0.000 claims description 5
• 208000032839 leukemia Diseases 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 125000004043 oxo group Chemical group O=* 0.000 claims description 5
• 125000003107 substituted aryl group Chemical group 0.000 claims description 5
• XXOQJWXDRPURJK-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1-benzoxepine Chemical group O1CCCCC2=CC=CC=C21 XXOQJWXDRPURJK-UHFFFAOYSA-N 0.000 claims description 4
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• 206010066476 Haematological malignancy Diseases 0.000 claims description 4
• 206010052779 Transplant rejections Diseases 0.000 claims description 4
• 208000006673 asthma Diseases 0.000 claims description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• KELIOZMTDOSCMM-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1-benzothiophene Chemical compound C1C=CC=C2SCCC21 KELIOZMTDOSCMM-UHFFFAOYSA-N 0.000 claims description 3
• WPWNEKFMGCWNPR-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromene Chemical compound C1=CC=C2CCCSC2=C1 WPWNEKFMGCWNPR-UHFFFAOYSA-N 0.000 claims description 3
• 230000001419 dependent effect Effects 0.000 claims description 3
• 201000005962 mycosis fungoides Diseases 0.000 claims description 3
• FRUWMYWEARDNTC-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-indole Chemical compound C1C=CC=C2NCCC21 FRUWMYWEARDNTC-UHFFFAOYSA-N 0.000 claims description 2
• 206010048396 Bone marrow transplant rejection Diseases 0.000 claims description 2
• 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 2
• 206010013774 Dry eye Diseases 0.000 claims description 2
• 208000009319 Keratoconjunctivitis Sicca Diseases 0.000 claims description 2
• 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 claims description 2
• 125000000068 chlorophenyl group Chemical group 0.000 claims description 2
• 201000007241 cutaneous T cell lymphoma Diseases 0.000 claims description 2
• 125000004212 difluorophenyl group Chemical group 0.000 claims description 2
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
• 201000005787 hematologic cancer Diseases 0.000 claims description 2
• 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 2
• 102000006500 Janus Kinase 3 Human genes 0.000 claims 2
• 108010019421 Janus Kinase 3 Proteins 0.000 claims 2
• KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims 2
• XRQNEEAAIUVDKC-UHFFFAOYSA-N 2,3-dihydro-1h-cyclopenta[b]pyridine;2,3,4,5-tetrahydro-1-benzoxepine Chemical group N1CCC=C2C=CC=C21.O1CCCCC2=CC=CC=C21 XRQNEEAAIUVDKC-UHFFFAOYSA-N 0.000 claims 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 1
• KTUADKLZRCMLJE-UHFFFAOYSA-N O1CCCC=C1.O1C=CC=C1 Chemical compound O1CCCC=C1.O1C=CC=C1 KTUADKLZRCMLJE-UHFFFAOYSA-N 0.000 claims 1
• 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims 1
• 125000003709 fluoroalkyl group Chemical group 0.000 claims 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims 1
• YNPFMWCWRVTGKJ-UHFFFAOYSA-N mianserin hydrochloride Chemical group [H+].[Cl-].C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 YNPFMWCWRVTGKJ-UHFFFAOYSA-N 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 209
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 175
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 151
• 239000000243 solution Substances 0.000 description 139
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 124
• 238000005160 1H NMR spectroscopy Methods 0.000 description 72
• 235000019439 ethyl acetate Nutrition 0.000 description 70
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 62
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 58
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
• 238000004440 column chromatography Methods 0.000 description 47
• 238000003786 synthesis reaction Methods 0.000 description 46
• 230000015572 biosynthetic process Effects 0.000 description 44
• 101150069380 JAK3 gene Proteins 0.000 description 32
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 29
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 28
• 239000012044 organic layer Substances 0.000 description 28
• 239000002904 solvent Substances 0.000 description 27
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
• 239000012267 brine Substances 0.000 description 24
• 239000000543 intermediate Substances 0.000 description 24
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
• 239000007787 solid Substances 0.000 description 22
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 20
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
• 238000006243 chemical reaction Methods 0.000 description 19
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 19
• QOWBXWFYRXSBAS-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C(OC)=C1 QOWBXWFYRXSBAS-UHFFFAOYSA-N 0.000 description 18
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 18
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 18
• 239000011734 sodium Substances 0.000 description 18
• HXACNHXAKSMYNU-UHFFFAOYSA-N 8-fluoro-3,4-dihydro-2h-chromen-4-amine Chemical compound C1=CC=C2C(N)CCOC2=C1F HXACNHXAKSMYNU-UHFFFAOYSA-N 0.000 description 17
• 239000000725 suspension Substances 0.000 description 17
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
• 239000000047 product Substances 0.000 description 16
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 15
• 238000010828 elution Methods 0.000 description 15
• 229920006395 saturated elastomer Polymers 0.000 description 15
• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
• 238000005481 NMR spectroscopy Methods 0.000 description 14
• 229910052786 argon Inorganic materials 0.000 description 14
• 239000000460 chlorine Substances 0.000 description 14
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 14
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 14
• 150000003839 salts Chemical class 0.000 description 13
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• 150000001412 amines Chemical class 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• 230000002829 reductive effect Effects 0.000 description 12
• 238000010992 reflux Methods 0.000 description 12
• 239000011780 sodium chloride Substances 0.000 description 12
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 11
• 210000004027 cell Anatomy 0.000 description 11
• 239000010410 layer Substances 0.000 description 11
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 11
• 235000017557 sodium bicarbonate Nutrition 0.000 description 11
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
• JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 11
• 229940123241 Janus kinase 3 inhibitor Drugs 0.000 description 10
• 239000002585 base Substances 0.000 description 10
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
• 229910000027 potassium carbonate Inorganic materials 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
• FKDMFDMYQZIZMI-UHFFFAOYSA-N 8-fluoro-2,3-dihydrochromen-4-one Chemical compound O=C1CCOC2=C1C=CC=C2F FKDMFDMYQZIZMI-UHFFFAOYSA-N 0.000 description 9
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 9
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• INUSQTPGSHFGHM-UHFFFAOYSA-N 2,4-dichloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1Cl INUSQTPGSHFGHM-UHFFFAOYSA-N 0.000 description 8
• UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 8
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
• 125000000753 cycloalkyl group Chemical group 0.000 description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
• 235000011181 potassium carbonates Nutrition 0.000 description 8
• 239000011541 reaction mixture Substances 0.000 description 8
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 7
• 208000009329 Graft vs Host Disease Diseases 0.000 description 7
• 108010002350 Interleukin-2 Proteins 0.000 description 7
• 102000000588 Interleukin-2 Human genes 0.000 description 7
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
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