JP5629324B2 - ピロロ［２，３−ｄ］ピリミジン化合物 - Google Patents

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Publication number

JP5629324B2

JP5629324B2 JP2012533715A JP2012533715A JP5629324B2 JP 5629324 B2 JP5629324 B2 JP 5629324B2 JP 2012533715 A JP2012533715 A JP 2012533715A JP 2012533715 A JP2012533715 A JP 2012533715A JP 5629324 B2 JP5629324 B2 JP 5629324B2

Authority

JP

Japan

Prior art keywords

group

methyl

alkyl

hydrogen

pyrrolo

Prior art date

2009-10-15

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.)

Expired - Fee Related

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• 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 title description 4
• -1 R 24 Chemical compound 0.000 claims description 259
• 150000001875 compounds Chemical class 0.000 claims description 204
• 229910052739 hydrogen Inorganic materials 0.000 claims description 189
• 239000001257 hydrogen Substances 0.000 claims description 188
• 150000003839 salts Chemical class 0.000 claims description 99
• 150000002431 hydrogen Chemical class 0.000 claims description 94
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 93
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 92
• 125000001424 substituent group Chemical group 0.000 claims description 90
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 71
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 70
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 54
• 125000003118 aryl group Chemical group 0.000 claims description 52
• 125000000623 heterocyclic group Chemical group 0.000 claims description 52
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 42
• 125000004076 pyridyl group Chemical group 0.000 claims description 40
• 125000001153 fluoro group Chemical group F* 0.000 claims description 39
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 37
• 108010024121 Janus Kinases Proteins 0.000 claims description 36
• 102000015617 Janus Kinases Human genes 0.000 claims description 36
• 125000005843 halogen group Chemical group 0.000 claims description 33
• 238000011282 treatment Methods 0.000 claims description 33
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 31
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
• VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims description 25
• 239000008194 pharmaceutical composition Substances 0.000 claims description 24
• 125000004043 oxo group Chemical group O=* 0.000 claims description 23
• 125000000217 alkyl group Chemical group 0.000 claims description 22
• 229910052757 nitrogen Inorganic materials 0.000 claims description 21
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 20
• 125000004193 piperazinyl group Chemical group 0.000 claims description 19
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 17
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 16
• 230000001404 mediated effect Effects 0.000 claims description 15
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• 208000006673 asthma Diseases 0.000 claims description 13
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 13
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 13
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 13
• 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 12
• 201000006417 multiple sclerosis Diseases 0.000 claims description 12
• 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 12
• 206010028980 Neoplasm Diseases 0.000 claims description 11
• 206010052779 Transplant rejections Diseases 0.000 claims description 11
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 10
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
• 208000023275 Autoimmune disease Diseases 0.000 claims description 9
• 201000010099 disease Diseases 0.000 claims description 9
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 9
• 210000000056 organ Anatomy 0.000 claims description 8
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
• 230000001363 autoimmune Effects 0.000 claims description 7
• 201000011510 cancer Diseases 0.000 claims description 7
• 206010012601 diabetes mellitus Diseases 0.000 claims description 7
• 125000003386 piperidinyl group Chemical group 0.000 claims description 7
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
• 206010020751 Hypersensitivity Diseases 0.000 claims description 6
• 125000003545 alkoxy group Chemical group 0.000 claims description 6
• 125000002393 azetidinyl group Chemical group 0.000 claims description 6
• 229910052799 carbon Inorganic materials 0.000 claims description 6
• 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 6
• 208000032839 leukemia Diseases 0.000 claims description 6
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
• 208000006011 Stroke Diseases 0.000 claims description 5
• 230000007815 allergy Effects 0.000 claims description 5
• 150000001412 amines Chemical class 0.000 claims description 5
• 125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 5
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
• DFVBZOPVGGDURA-UYSNPLJNSA-N (3r)-1-[[4-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylsulfonyl]piperidin-3-ol Chemical compound N=1C=NC=2NC=CC=2C=1N(C)C(CC1)CCC1CS(=O)(=O)N1CCC[C@@H](O)C1 DFVBZOPVGGDURA-UYSNPLJNSA-N 0.000 claims description 4
• 208000024827 Alzheimer disease Diseases 0.000 claims description 4
• QMHIFZZTSBMKGF-NXOAAHMSSA-N C1[C@H](CO)[C@@H](C)CN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 Chemical compound C1[C@H](CO)[C@@H](C)CN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 QMHIFZZTSBMKGF-NXOAAHMSSA-N 0.000 claims description 4
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
• 206010025323 Lymphomas Diseases 0.000 claims description 4
• 201000004681 Psoriasis Diseases 0.000 claims description 4
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
• 208000026935 allergic disease Diseases 0.000 claims description 4
• 206010003246 arthritis Diseases 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• UCALNVLMEPQUKV-SOAGJPPSSA-N diethyl [(3r)-1-[[4-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylsulfonyl]piperidin-3-yl] phosphate Chemical compound C1[C@H](OP(=O)(OCC)OCC)CCCN1S(=O)(=O)CC1CCC(N(C)C=2C=3C=CNC=3N=CN=2)CC1 UCALNVLMEPQUKV-SOAGJPPSSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 4
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
• CNUBKBHAGWYWKC-QAQDUYKDSA-N C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCC(CO)CC1 Chemical compound C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCC(CO)CC1 CNUBKBHAGWYWKC-QAQDUYKDSA-N 0.000 claims description 3
• PLALKTRHBMUZHB-ORXZLVCASA-N C1C(OCC(C)C)CCCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 Chemical compound C1C(OCC(C)C)CCCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 PLALKTRHBMUZHB-ORXZLVCASA-N 0.000 claims description 3
• NCZZXIYJRYNEAO-GAZRBOARSA-N C1C(OCCOC)CCCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 Chemical compound C1C(OCCOC)CCCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 NCZZXIYJRYNEAO-GAZRBOARSA-N 0.000 claims description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
• 208000011231 Crohn disease Diseases 0.000 claims description 3
• 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 3
• 206010013774 Dry eye Diseases 0.000 claims description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
• 208000014767 Myeloproliferative disease Diseases 0.000 claims description 3
• COJRADVRHGSQAO-GUDVDZBRSA-N N1C[C@H](CCC1)CC(C(=O)OS(=O)(=O)C[C@@H]1CC[C@H](CC1)N(C=1C2=C(N=CN1)NC=C2)C)(C)C Chemical compound N1C[C@H](CCC1)CC(C(=O)OS(=O)(=O)C[C@@H]1CC[C@H](CC1)N(C=1C2=C(N=CN1)NC=C2)C)(C)C COJRADVRHGSQAO-GUDVDZBRSA-N 0.000 claims description 3
• 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 claims description 3
• 206010060862 Prostate cancer Diseases 0.000 claims description 3
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 3
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 3
• 206010040047 Sepsis Diseases 0.000 claims description 3
• 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 claims description 3
• 210000001744 T-lymphocyte Anatomy 0.000 claims description 3
• 206010046851 Uveitis Diseases 0.000 claims description 3
• GYZPAKVHBCQCKK-HVEGKCCWSA-N [(3s)-1-[[3-methyl-4-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylsulfonyl]pyrrolidin-3-yl]methanol Chemical compound C1CC(N(C)C=2C=3C=CNC=3N=CN=2)C(C)CC1CS(=O)(=O)N1CC[C@H](CO)C1 GYZPAKVHBCQCKK-HVEGKCCWSA-N 0.000 claims description 3
• 206010006451 bronchitis Diseases 0.000 claims description 3
• 208000027866 inflammatory disease Diseases 0.000 claims description 3
• 201000008482 osteoarthritis Diseases 0.000 claims description 3
• 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 claims description 2
• QUUQHDKVPKLLLY-SHTZXODSSA-N C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCC(O)CC1 Chemical compound C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCC(O)CC1 QUUQHDKVPKLLLY-SHTZXODSSA-N 0.000 claims description 2
• JRSQFRIEIAFSCP-XUWMOKQASA-N C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCCC(CO)C1 Chemical compound C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCCC(CO)C1 JRSQFRIEIAFSCP-XUWMOKQASA-N 0.000 claims description 2
• DFVBZOPVGGDURA-MRJYIUEKSA-N C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCCC(O)C1 Chemical compound C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCCC(O)C1 DFVBZOPVGGDURA-MRJYIUEKSA-N 0.000 claims description 2
• DFVBZOPVGGDURA-JYJNAYRXSA-N C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCC[C@H](O)C1 Chemical compound C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCC[C@H](O)C1 DFVBZOPVGGDURA-JYJNAYRXSA-N 0.000 claims description 2
• MALGNVZPLRYZHA-NXNVCVFFSA-N C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CC[C@H](O)[C@H](O)C1 Chemical compound C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CC[C@H](O)[C@H](O)C1 MALGNVZPLRYZHA-NXNVCVFFSA-N 0.000 claims description 2
• RCKHTJNDTULILG-RRCSTGOVSA-N C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1C[C@@H](F)[C@H](F)C1 Chemical compound C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1C[C@@H](F)[C@H](F)C1 RCKHTJNDTULILG-RRCSTGOVSA-N 0.000 claims description 2
• HLXPYAHSGDXUCD-XUWMOKQASA-N C1C(COC)CCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 Chemical compound C1C(COC)CCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 HLXPYAHSGDXUCD-XUWMOKQASA-N 0.000 claims description 2
• VKZZRIHGEAOOMI-BDWYFLKXSA-N C1C(OC)CCCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 Chemical compound C1C(OC)CCCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 VKZZRIHGEAOOMI-BDWYFLKXSA-N 0.000 claims description 2
• QBEUWGUQNWOOHV-JHJOSGQCSA-N C1C(OCC)CCCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 Chemical compound C1C(OCC)CCCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 QBEUWGUQNWOOHV-JHJOSGQCSA-N 0.000 claims description 2
• CZGHFDUUBKBTJH-IYARVYRRSA-N C1CC(COC)CCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 Chemical compound C1CC(COC)CCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 CZGHFDUUBKBTJH-IYARVYRRSA-N 0.000 claims description 2
• PKPFNPHDHKBHHB-WKILWMFISA-N C1CC(OC)CCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 Chemical compound C1CC(OC)CCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 PKPFNPHDHKBHHB-WKILWMFISA-N 0.000 claims description 2
• ZJVHOOYSNPZCAM-BZUAXINKSA-N C1[C@H](OC)CCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 Chemical compound C1[C@H](OC)CCN1S(=O)(=O)C[C@@H]1CC[C@@H](N(C)C=2C=3C=CNC=3N=CN=2)CC1 ZJVHOOYSNPZCAM-BZUAXINKSA-N 0.000 claims description 2
• 208000034578 Multiple myelomas Diseases 0.000 claims description 2
• 201000007224 Myeloproliferative neoplasm Diseases 0.000 claims description 2
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
• 208000024799 Thyroid disease Diseases 0.000 claims description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
• 238000010322 bone marrow transplantation Methods 0.000 claims description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
• 206010025135 lupus erythematosus Diseases 0.000 claims description 2
• 125000006626 methoxycarbonylamino group Chemical group 0.000 claims description 2
• 125000006405 methylpyridazinyl group Chemical group 0.000 claims description 2
• 230000003612 virological effect Effects 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 11
• JHPKJBVRIXKCRE-UHFFFAOYSA-N 2-sulfonylpiperidin-3-ol Chemical compound S(=O)(=O)=C1NCCCC1O JHPKJBVRIXKCRE-UHFFFAOYSA-N 0.000 claims 2
• 238000010276 construction Methods 0.000 claims 2
• CTSSTHCUMHCFMF-RRCSTGOVSA-N C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1C[C@@H](O)[C@H](O)C1 Chemical compound C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1C[C@@H](O)[C@H](O)C1 CTSSTHCUMHCFMF-RRCSTGOVSA-N 0.000 claims 1
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 1
• 125000000392 cycloalkenyl group Chemical group 0.000 claims 1
• IZXWMVPZODQBRB-UHFFFAOYSA-N piperidine-3,4-diol Chemical compound OC1CCNCC1O IZXWMVPZODQBRB-UHFFFAOYSA-N 0.000 claims 1
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims 1
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
• 239000000203 mixture Substances 0.000 description 93
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• 238000000034 method Methods 0.000 description 46
• 239000011541 reaction mixture Substances 0.000 description 45
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• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 34
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• 239000000243 solution Substances 0.000 description 30
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
• 239000007787 solid Substances 0.000 description 28
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 27
• 238000006243 chemical reaction Methods 0.000 description 25
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• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
• 239000002904 solvent Substances 0.000 description 22
• 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 21
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