JP2014513703A - 新規ヘキサヒドロシクロペンタピロロン、ヘキサヒドロピロロピロロン、オクタヒドロピロロピリジノン及びオクタヒドロピリジノン化合物 - Google Patents

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Publication number

JP2014513703A

JP2014513703A JP2014510758A JP2014510758A JP2014513703A JP 2014513703 A JP2014513703 A JP 2014513703A JP 2014510758 A JP2014510758 A JP 2014510758A JP 2014510758 A JP2014510758 A JP 2014510758A JP 2014513703 A JP2014513703 A JP 2014513703A

Authority

JP

Japan

Prior art keywords

phenyl

trifluoromethoxy

pyrrolo

octahydro

substituted

Prior art date

2011-05-17

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.)

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 203
• DSILUGCORMLHPA-UHFFFAOYSA-N 2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,2-b]pyrrol-5-one Chemical compound N1CCC2NC(=O)CC21 DSILUGCORMLHPA-UHFFFAOYSA-N 0.000 title 1
• PMGSPDVTAKHCLW-UHFFFAOYSA-N 3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[b]pyrrol-2-one Chemical compound C1CCC2NC(=O)CC21 PMGSPDVTAKHCLW-UHFFFAOYSA-N 0.000 title 1
• 238000000034 method Methods 0.000 claims abstract description 52
• -1 haloalkoxy compound Chemical class 0.000 claims description 83
• 125000000217 alkyl group Chemical group 0.000 claims description 56
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 56
• 230000002265 prevention Effects 0.000 claims description 49
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
• 206010012601 diabetes mellitus Diseases 0.000 claims description 28
• 229910052739 hydrogen Inorganic materials 0.000 claims description 28
• 239000001257 hydrogen Substances 0.000 claims description 28
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 28
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 25
• 150000003839 salts Chemical class 0.000 claims description 25
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
• 125000003545 alkoxy group Chemical group 0.000 claims description 21
• 201000001320 Atherosclerosis Diseases 0.000 claims description 20
• 208000008589 Obesity Diseases 0.000 claims description 20
• 230000004064 dysfunction Effects 0.000 claims description 20
• 235000020824 obesity Nutrition 0.000 claims description 20
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 19
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 19
• 206010061218 Inflammation Diseases 0.000 claims description 19
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 19
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 19
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 19
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 19
• 230000004054 inflammatory process Effects 0.000 claims description 19
• 230000002107 myocardial effect Effects 0.000 claims description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 18
• 150000002367 halogens Chemical group 0.000 claims description 18
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
• 239000003814 drug Substances 0.000 claims description 16
• 125000001072 heteroaryl group Chemical group 0.000 claims description 16
• 102000000019 Sterol Esterase Human genes 0.000 claims description 15
• 108010055297 Sterol Esterase Proteins 0.000 claims description 15
• 125000001424 substituent group Chemical group 0.000 claims description 15
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• 150000002431 hydrogen Chemical class 0.000 claims description 14
• 125000005359 phenoxyalkyl group Chemical group 0.000 claims description 14
• 238000002360 preparation method Methods 0.000 claims description 14
• 125000001188 haloalkyl group Chemical group 0.000 claims description 13
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
• 125000004076 pyridyl group Chemical group 0.000 claims description 12
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 12
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 10
• 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 9
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 8
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
• 230000008569 process Effects 0.000 claims description 7
• TZYWCWPNWKEQCG-ANEWXZNUSA-N (3ar,7as)-2-[2-(2,4-dichlorophenyl)-2-hydroxyethyl]-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C([C@@H]1CN(C[C@@H]1C1=O)CC(O)C=2C(=CC(Cl)=CC=2)Cl)CN1C1=CC=C(OCC(F)(F)F)C=C1 TZYWCWPNWKEQCG-ANEWXZNUSA-N 0.000 claims description 4
• OOPXPUHSUWIQHN-PBHICJAKSA-N (3ar,7as)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-2-[2-(trifluoromethoxy)phenyl]sulfonyl-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@H]2CN(S(=O)(=O)C=3C(=CC=CC=3)OC(F)(F)F)C[C@H]2CC1 OOPXPUHSUWIQHN-PBHICJAKSA-N 0.000 claims description 4
• ICURKDZAOKAZKG-OWQGQXMQSA-N (3as,5s,6ar)-5-(butoxymethyl)-5-hydroxy-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@H]1C[C@@](C[C@@H]1C1=O)(O)COCCCC)N1C1=CC=C(OC(F)(F)F)C=C1 ICURKDZAOKAZKG-OWQGQXMQSA-N 0.000 claims description 4
• RUZIVNMLRPKBGI-KUBVQFIISA-N (3as,7ar)-1-(2-phenylacetyl)-5-[4-(trifluoromethoxy)phenyl]-2,3,3a,6,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)[C@H](CNC2C(=O)CC=3C=CC=CC=3)[C@H]2CC1 RUZIVNMLRPKBGI-KUBVQFIISA-N 0.000 claims description 4
• IOHFWOZJENTFLA-XJKSGUPXSA-N (3as,7ar)-2-(2-chlorophenyl)sulfonyl-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)[C@@H]2CN(S(=O)(=O)C=3C(=CC=CC=3)Cl)C[C@@H]2CC1 IOHFWOZJENTFLA-XJKSGUPXSA-N 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 239000013543 active substance Substances 0.000 claims description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• ZCLNJVVEHPLNDO-BSBHGOPBSA-N n-[(3as,6ar)-3-oxo-2-[4-(trifluoromethoxy)phenyl]-1,3a,4,5,6,6a-hexahydrocyclopenta[c]pyrrol-5-yl]-2-chlorobenzenesulfonamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)[C@H]2CC(NS(=O)(=O)C=3C(=CC=CC=3)Cl)C[C@H]2C1 ZCLNJVVEHPLNDO-BSBHGOPBSA-N 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims description 3
• SDRXORFVMCHESD-CHEUHSMRSA-N (3ar,7as)-1-(2-phenylacetyl)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-2,3,3a,6,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@@H](CNC2C(=O)CC=3C=CC=CC=3)[C@@H]2CC1 SDRXORFVMCHESD-CHEUHSMRSA-N 0.000 claims description 2
• JWCAWYZVCBQCHU-PBHICJAKSA-N (3ar,7as)-2-(2-chlorophenyl)sulfonyl-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@H]2CN(S(=O)(=O)C=3C(=CC=CC=3)Cl)C[C@H]2CC1 JWCAWYZVCBQCHU-PBHICJAKSA-N 0.000 claims description 2
• URZPTRWITOLAHH-CJNGLKHVSA-N (3ar,7as)-2-(2-chloropyridin-3-yl)sulfonyl-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@H]2CN(S(=O)(=O)C=3C(=NC=CC=3)Cl)C[C@H]2CC1 URZPTRWITOLAHH-CJNGLKHVSA-N 0.000 claims description 2
• UTIMXNSQVSYIOG-PBHICJAKSA-N (3ar,7as)-2-(2-hydroxyphenyl)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound OC1=CC=CC=C1N1C[C@@H]2C(=O)N(C=3C=CC(OCC(F)(F)F)=CC=3)CC[C@@H]2C1 UTIMXNSQVSYIOG-PBHICJAKSA-N 0.000 claims description 2
• TUTZPAJFLXAIQH-PBHICJAKSA-N (3ar,7as)-2-(3,3-dimethylbutanoyl)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C([C@@H]1CN(C[C@@H]1C1=O)C(=O)CC(C)(C)C)CN1C1=CC=C(OCC(F)(F)F)C=C1 TUTZPAJFLXAIQH-PBHICJAKSA-N 0.000 claims description 2
• QLGSFDRAOBTLSJ-BEFAXECRSA-N (3ar,7as)-2-(benzenesulfonyl)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@H]2CN(S(=O)(=O)C=3C=CC=CC=3)C[C@H]2CC1 QLGSFDRAOBTLSJ-BEFAXECRSA-N 0.000 claims description 2
• VUKYNERAKZLTOZ-UZLBHIALSA-N (3ar,7as)-2-[2-(4-fluorophenyl)acetyl]-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(F)=CC=C1CC(=O)N1C[C@@H]2C(=O)N(C=3C=CC(OCC(F)(F)F)=CC=3)CC[C@@H]2C1 VUKYNERAKZLTOZ-UZLBHIALSA-N 0.000 claims description 2
• BMTUEDGSYHQHFI-NQIIRXRSSA-N (3ar,7as)-2-[2-(4-methylphenyl)acetyl]-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(C)=CC=C1CC(=O)N1C[C@@H]2C(=O)N(C=3C=CC(OCC(F)(F)F)=CC=3)CC[C@@H]2C1 BMTUEDGSYHQHFI-NQIIRXRSSA-N 0.000 claims description 2
• BWVIKPJQQKIUGB-PBHICJAKSA-N (3ar,7as)-5-[4-(2,2,2-trifluoroethoxy)phenyl]-2-[2-(trifluoromethyl)phenyl]sulfonyl-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OCC(F)(F)F)=CC=C1N1C(=O)[C@H]2CN(S(=O)(=O)C=3C(=CC=CC=3)C(F)(F)F)C[C@H]2CC1 BWVIKPJQQKIUGB-PBHICJAKSA-N 0.000 claims description 2
• ZOSXIEYYQRCFQH-XEGUGMAKSA-N (3as,5s,6ar)-5-hydroxy-5-(2,2,2-trifluoroethoxymethyl)-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@H]1C[C@](C[C@@H]1C1=O)(COCC(F)(F)F)O)N1C1=CC=C(OC(F)(F)F)C=C1 ZOSXIEYYQRCFQH-XEGUGMAKSA-N 0.000 claims description 2
• FWMIDUCEURWGLJ-DCPHZVHLSA-N (3as,5s,6ar)-5-hydroxy-5-(phenoxymethyl)-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@]1(O)C[C@@H]2C(=O)N(C[C@@H]2C1)C=1C=CC(OC(F)(F)F)=CC=1)OC1=CC=CC=C1 FWMIDUCEURWGLJ-DCPHZVHLSA-N 0.000 claims description 2
• UQTFGVGNOYPZBT-NUTKFTJISA-N (3as,5s,6ar)-5-hydroxy-5-(propoxymethyl)-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@H]1C[C@@](C[C@@H]1C1=O)(O)COCCC)N1C1=CC=C(OC(F)(F)F)C=C1 UQTFGVGNOYPZBT-NUTKFTJISA-N 0.000 claims description 2
• JQQBOTWLJXCTBZ-KEXXGOCASA-N (3as,6ar)-5-(anilinomethyl)-5-hydroxy-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@H]1C(=O)N(C[C@@H]1C1)C=2C=CC(OC(F)(F)F)=CC=2)C1(O)CNC1=CC=CC=C1 JQQBOTWLJXCTBZ-KEXXGOCASA-N 0.000 claims description 2
• SNVFIFXXEAAXLK-XPFLZZBLSA-N (3as,6ar)-5-hydroxy-5-propyl-2-[4-(trifluoromethoxy)phenyl]-3a,4,6,6a-tetrahydro-1h-cyclopenta[c]pyrrol-3-one Chemical compound C([C@@H]1CC(C[C@@H]1C1=O)(O)CCC)N1C1=CC=C(OC(F)(F)F)C=C1 SNVFIFXXEAAXLK-XPFLZZBLSA-N 0.000 claims description 2
• BVXPXCFIGDWPIB-DNVCBOLYSA-N (3as,6as)-5-(4-ethylphenyl)-4-oxo-n-[4-(trifluoromethoxy)phenyl]-3,3a,6,6a-tetrahydro-1h-pyrrolo[3,4-c]pyrrole-2-carboxamide Chemical compound C1=CC(CC)=CC=C1N1C(=O)[C@@H]2CN(C(=O)NC=3C=CC(OC(F)(F)F)=CC=3)C[C@@H]2C1 BVXPXCFIGDWPIB-DNVCBOLYSA-N 0.000 claims description 2
• UTWATDQGGKALAL-SUMWQHHRSA-N (3as,7ar)-2-(2-chlorobenzoyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)[C@@H]2CN(C(=O)C=3C(=CC=CC=3)Cl)C[C@@H]2CC1 UTWATDQGGKALAL-SUMWQHHRSA-N 0.000 claims description 2
• YXAQHOMOMXWBST-XJKSGUPXSA-N (3as,7ar)-2-(2-methylpropylsulfonyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C([C@H]1CN(C[C@H]1C1=O)S(=O)(=O)CC(C)C)CN1C1=CC=C(OC(F)(F)F)C=C1 YXAQHOMOMXWBST-XJKSGUPXSA-N 0.000 claims description 2
• FIADIBYFRWITEN-XJKSGUPXSA-N (3as,7ar)-2-(3-methylbutanoyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C([C@H]1CN(C[C@H]1C1=O)C(=O)CC(C)C)CN1C1=CC=C(OC(F)(F)F)C=C1 FIADIBYFRWITEN-XJKSGUPXSA-N 0.000 claims description 2
• TWMYWSDGOVHDKS-WMLDXEAASA-N (3as,7ar)-2-(3-methylbutylsulfonyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C([C@H]1CN(C[C@H]1C1=O)S(=O)(=O)CCC(C)C)CN1C1=CC=C(OC(F)(F)F)C=C1 TWMYWSDGOVHDKS-WMLDXEAASA-N 0.000 claims description 2
• MFAMMXPGEWSZTR-KBXCAEBGSA-N (3as,7ar)-2-(4-fluorobenzoyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 MFAMMXPGEWSZTR-KBXCAEBGSA-N 0.000 claims description 2
• WPSQOKLLQVOTBZ-SCLBCKFNSA-N (3as,7ar)-2-(4-fluorophenyl)sulfonyl-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(F)=CC=C1S(=O)(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 WPSQOKLLQVOTBZ-SCLBCKFNSA-N 0.000 claims description 2
• UVQXTGZXMGDYMH-GHTZIAJQSA-N (3as,7ar)-2-(4-propan-2-ylbenzoyl)-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(C(C)C)=CC=C1C(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 UVQXTGZXMGDYMH-GHTZIAJQSA-N 0.000 claims description 2
• DXVHIIDHQSBIDF-HNAYVOBHSA-N (3as,7ar)-2-[(4-fluorophenyl)methyl]-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(F)=CC=C1CN1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 DXVHIIDHQSBIDF-HNAYVOBHSA-N 0.000 claims description 2
• ABDCELHRYJDOPX-QFBILLFUSA-N (3as,7ar)-2-benzylsulfonyl-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-4-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)[C@@H]2CN(S(=O)(=O)CC=3C=CC=CC=3)C[C@@H]2CC1 ABDCELHRYJDOPX-QFBILLFUSA-N 0.000 claims description 2
• VTFOQHWGMPFGSF-SCLBCKFNSA-N (3as,7ar)-4-oxo-n,5-bis[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 VTFOQHWGMPFGSF-SCLBCKFNSA-N 0.000 claims description 2
• RPGIAZHLHQUFBN-SCLBCKFNSA-N (3as,7ar)-n-(4-fluorophenyl)-4-oxo-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)N1C[C@H]2C(=O)N(C=3C=CC(OC(F)(F)F)=CC=3)CC[C@H]2C1 RPGIAZHLHQUFBN-SCLBCKFNSA-N 0.000 claims description 2
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
• SDRNBXQJIXBCGH-QWLMFLSESA-N 2-[(3ar,7as)-4-oxo-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridin-2-yl]-n-(4-fluorophenyl)-3-methylbutanamide Chemical compound C([C@@H]1CN(C[C@@H]1C1=O)C(C(C)C)C(=O)NC=2C=CC(F)=CC=2)CN1C1=CC=C(OCC(F)(F)F)C=C1 SDRNBXQJIXBCGH-QWLMFLSESA-N 0.000 claims description 2
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
• 208000035475 disorder Diseases 0.000 claims description 2
• NYMDZLNOQPHCMN-CJNGLKHVSA-N tert-butyl (3ar,7as)-4-oxo-5-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridine-2-carboxylate Chemical compound C([C@@H]1CN(C[C@@H]1C1=O)C(=O)OC(C)(C)C)CN1C1=CC=C(OCC(F)(F)F)C=C1 NYMDZLNOQPHCMN-CJNGLKHVSA-N 0.000 claims description 2
• LMSUQMJAMATPBV-DOMZBBRYSA-N tert-butyl (3ar,7as)-4-oxo-5-[4-(trifluoromethoxy)phenyl]-1,3,3a,6,7,7a-hexahydropyrrolo[3,4-c]pyridine-2-carboxylate Chemical compound C([C@@H]1CN(C[C@@H]1C1=O)C(=O)OC(C)(C)C)CN1C1=CC=C(OC(F)(F)F)C=C1 LMSUQMJAMATPBV-DOMZBBRYSA-N 0.000 claims description 2
• AGYMBTDCKVMYIT-UHFFFAOYSA-N FC(OC1=CC=C(C=C1)NC(=O)N1C(C2CNCC2C1)C1=CC=C(C=C1)OC(F)(F)F)(F)F Chemical compound FC(OC1=CC=C(C=C1)NC(=O)N1C(C2CNCC2C1)C1=CC=C(C=C1)OC(F)(F)F)(F)F AGYMBTDCKVMYIT-UHFFFAOYSA-N 0.000 claims 1
• 201000010099 disease Diseases 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 60
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 100
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 86
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 57
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
• 238000005481 NMR spectroscopy Methods 0.000 description 53
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
• 239000000243 solution Substances 0.000 description 31
• 235000019439 ethyl acetate Nutrition 0.000 description 30
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
• 230000015572 biosynthetic process Effects 0.000 description 27
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