RU2603191C2 - 3-ОКСО-3,9-ДИГИДРО-1Н-ХРОМЕНО[2,3-c]ПИРРОЛЫ В КАЧЕСТВЕ АКТИВАТОРОВ ГЛЮКОКИНАЗЫ - Google Patents

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Publication number

RU2603191C2

RU2603191C2 RU2012156706/04A RU2012156706A RU2603191C2 RU 2603191 C2 RU2603191 C2 RU 2603191C2 RU 2012156706/04 A RU2012156706/04 A RU 2012156706/04A RU 2012156706 A RU2012156706 A RU 2012156706A RU 2603191 C2 RU2603191 C2 RU 2603191C2

Authority

RU

Russia

Prior art keywords

dihydro

oxo

chromeno

pyrrol

methyl

Prior art date

2010-06-17

Links

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• 102000030595 Glucokinase Human genes 0.000 title claims description 15
• 108010021582 Glucokinase Proteins 0.000 title claims description 15
• 239000012190 activator Substances 0.000 title description 7
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 233
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 70
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 41
• 150000003839 salts Chemical class 0.000 claims abstract description 41
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 33
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 32
• 238000000034 method Methods 0.000 claims abstract description 32
• 150000001721 carbon Chemical group 0.000 claims abstract description 20
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 20
• 229910052801 chlorine Inorganic materials 0.000 claims abstract description 15
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
• 150000002367 halogens Chemical class 0.000 claims abstract description 14
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
• 208000030159 metabolic disease Diseases 0.000 claims abstract description 14
• 125000003277 amino group Chemical group 0.000 claims abstract description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 10
• 201000010099 disease Diseases 0.000 claims abstract description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 7
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 5
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 5
• 229910052794 bromium Inorganic materials 0.000 claims abstract description 4
• -1 5-chloro-pyridin-2-yl Chemical group 0.000 claims description 467
• 239000000203 mixture Substances 0.000 claims description 55
• 238000011282 treatment Methods 0.000 claims description 19
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 16
• YCPFQYGGDDPZBJ-ZDUSSCGKSA-N (2s)-2-(5,8-dimethoxy-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-4-methylpentanoic acid Chemical compound C1C=2C(OC)=CC=C(OC)C=2OC2=C1CN([C@@H](CC(C)C)C(O)=O)C2=O YCPFQYGGDDPZBJ-ZDUSSCGKSA-N 0.000 claims description 11
• 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 11
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
• 125000004076 pyridyl group Chemical group 0.000 claims description 10
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
• 125000000034 thioazolyl group Chemical group 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 6
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 6
• 229940080818 propionamide Drugs 0.000 claims description 6
• CGSWQZWTNQZWNF-KRWDZBQOSA-N (2s)-n-(5-chloropyridin-2-yl)-2-(5,8-dimethoxy-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-4-methylpentanamide Chemical compound O=C([C@H](CC(C)C)N1CC2=C(C1=O)OC=1C(OC)=CC=C(C=1C2)OC)NC1=CC=C(Cl)C=N1 CGSWQZWTNQZWNF-KRWDZBQOSA-N 0.000 claims description 5
• ZGQKUSRLSNZSAZ-SFHVURJKSA-N (2s)-2-(5-chloro-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C([C@H](N1C(=O)C2=C(C1)CC=1C=CC=C(C=1O2)Cl)C(=O)NC=1SC=CN=1)C1CCCCC1 ZGQKUSRLSNZSAZ-SFHVURJKSA-N 0.000 claims description 4
• DDWDSGPCZOUOIV-FQEVSTJZSA-N (2s)-2-(5-chloro-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-n-pyridin-2-ylpropanamide Chemical compound C([C@H](N1C(=O)C2=C(C1)CC=1C=CC=C(C=1O2)Cl)C(=O)NC=1N=CC=CC=1)C1CCCCC1 DDWDSGPCZOUOIV-FQEVSTJZSA-N 0.000 claims description 4
• YWKFGOWRGVXVRX-KRWDZBQOSA-N (2s)-2-(5-chloro-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-4-methyl-n-pyridin-2-ylpentanamide Chemical compound O=C([C@@H](N1C(C2=C(CC3=CC=CC(Cl)=C3O2)C1)=O)CC(C)C)NC1=CC=CC=N1 YWKFGOWRGVXVRX-KRWDZBQOSA-N 0.000 claims description 4
• KODSXHNGZNXMHC-SFHVURJKSA-N (2s)-2-(8-chloro-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C([C@H](N1CC2=C(C1=O)OC=1C=CC=C(C=1C2)Cl)C(=O)NC=1SC=CN=1)C1CCCCC1 KODSXHNGZNXMHC-SFHVURJKSA-N 0.000 claims description 4
• WEEKKOREMIGRDV-FQEVSTJZSA-N (2s)-2-(8-chloro-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-n-pyridin-2-ylpropanamide Chemical compound C([C@H](N1CC2=C(C1=O)OC=1C=CC=C(C=1C2)Cl)C(=O)NC=1N=CC=CC=1)C1CCCCC1 WEEKKOREMIGRDV-FQEVSTJZSA-N 0.000 claims description 4
• HBSUMLZMJTZGBT-KRWDZBQOSA-N (2s)-2-(8-chloro-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-n-(5-chloropyridin-2-yl)-4-methylpentanamide Chemical compound O=C([C@@H](N1C(C2=C(CC3=C(Cl)C=CC=C3O2)C1)=O)CC(C)C)NC1=CC=C(Cl)C=N1 HBSUMLZMJTZGBT-KRWDZBQOSA-N 0.000 claims description 4
• OREFYHQAZOLNIE-SFHVURJKSA-N (2s)-3-cyclohexyl-2-(8-methoxy-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C([C@H](N1CC2=C(C1=O)OC=1C=CC=C(C=1C2)OC)C(=O)NC=1SC=CN=1)C1CCCCC1 OREFYHQAZOLNIE-SFHVURJKSA-N 0.000 claims description 4
• UTYJLKOOXXNAFD-FQEVSTJZSA-N (2s)-3-cyclohexyl-2-(8-methoxy-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-n-pyridin-2-ylpropanamide Chemical compound C([C@H](N1CC2=C(C1=O)OC=1C=CC=C(C=1C2)OC)C(=O)NC=1N=CC=CC=1)C1CCCCC1 UTYJLKOOXXNAFD-FQEVSTJZSA-N 0.000 claims description 4
• UCLWFNCLGOWCAZ-CTNGQTDRSA-N (2s)-3-cyclohexyl-n-[1-[(2r)-2,3-dihydroxypropyl]pyrazol-3-yl]-2-(8-methoxy-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)propanamide Chemical compound C([C@H](N1CC2=C(C1=O)OC=1C=CC=C(C=1C2)OC)C(=O)NC1=NN(C[C@@H](O)CO)C=C1)C1CCCCC1 UCLWFNCLGOWCAZ-CTNGQTDRSA-N 0.000 claims description 4
• RKPPPKVKKAMZMQ-FQEVSTJZSA-N (2s)-3-cyclopentyl-n-[1-(2-hydroxy-2-methylpropyl)pyrazol-3-yl]-2-(3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)propanamide Chemical compound CC(C)(O)CN1C=CC(NC(=O)[C@H](CC2CCCC2)N2C(C3=C(CC4=CC=CC=C4O3)C2)=O)=N1 RKPPPKVKKAMZMQ-FQEVSTJZSA-N 0.000 claims description 4
• QSWSHRPPPUYIDY-FQEVSTJZSA-N (2s)-n-(5-chloropyridin-2-yl)-3-cyclohexyl-2-(5,8-dimethoxy-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)propanamide Chemical compound C([C@H](N1CC2=C(C1=O)OC=1C(OC)=CC=C(C=1C2)OC)C(=O)NC=1N=CC(Cl)=CC=1)C1CCCCC1 QSWSHRPPPUYIDY-FQEVSTJZSA-N 0.000 claims description 4
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
• USWJTLZIOPWSHR-SFHVURJKSA-N methyl 6-[[(2s)-2-(5,8-dimethoxy-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-4-methylpentanoyl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC(=O)[C@H](CC(C)C)N1C(=O)C(OC=2C(=C(OC)C=CC=2OC)C2)=C2C1 USWJTLZIOPWSHR-SFHVURJKSA-N 0.000 claims description 4
• IKMJOSYSAQJYKR-NRFANRHFSA-N methyl 6-[[(2s)-3-cyclohexyl-2-(5,8-dimethoxy-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)propanoyl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC(=O)[C@@H](N1C(C2=C(CC3=C(OC)C=CC(OC)=C3O2)C1)=O)CC1CCCCC1 IKMJOSYSAQJYKR-NRFANRHFSA-N 0.000 claims description 4
• GAUIONMVLNGSKI-HNNXBMFYSA-N (2s)-2-(5-chloro-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-4-methyl-n-(1,3-thiazol-2-yl)pentanamide Chemical compound O=C([C@@H](N1C(C2=C(CC3=CC=CC(Cl)=C3O2)C1)=O)CC(C)C)NC1=NC=CS1 GAUIONMVLNGSKI-HNNXBMFYSA-N 0.000 claims description 3
• FNNWHXSUOJRBJO-KRWDZBQOSA-N (2s)-2-(8-chloro-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-4-methyl-n-pyridin-2-ylpentanamide Chemical compound O=C([C@@H](N1C(C2=C(CC3=C(Cl)C=CC=C3O2)C1)=O)CC(C)C)NC1=CC=CC=N1 FNNWHXSUOJRBJO-KRWDZBQOSA-N 0.000 claims description 3
• ZFITUKKMKFQVOV-HNNXBMFYSA-N (2s)-2-(8-methoxy-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-4-methyl-n-(1,3-thiazol-2-yl)pentanamide Chemical compound O=C([C@H](CC(C)C)N1CC2=C(C1=O)OC=1C=CC=C(C=1C2)OC)NC1=NC=CS1 ZFITUKKMKFQVOV-HNNXBMFYSA-N 0.000 claims description 3
• UXYYPLSWBNEUFA-KRWDZBQOSA-N CC(C)C[C@@H](C(NC(C=C1)=NC=C1C(O)=O)=O)N(CC(C1)=C2OC3=C1C(Cl)=CC=C3)C2=O Chemical compound CC(C)C[C@@H](C(NC(C=C1)=NC=C1C(O)=O)=O)N(CC(C1)=C2OC3=C1C(Cl)=CC=C3)C2=O UXYYPLSWBNEUFA-KRWDZBQOSA-N 0.000 claims description 3
• NMABCXQUJAUYAN-KRWDZBQOSA-N CC(C)C[C@@H](C(NC(C=C1)=NC=C1C(O)=O)=O)N(CC(C1)=C2OC3=C1C(OC)=CC=C3)C2=O Chemical compound CC(C)C[C@@H](C(NC(C=C1)=NC=C1C(O)=O)=O)N(CC(C1)=C2OC3=C1C(OC)=CC=C3)C2=O NMABCXQUJAUYAN-KRWDZBQOSA-N 0.000 claims description 3
• REHAXDQHKSUAPJ-KRWDZBQOSA-N CC(C)C[C@@H](C(NC(C=C1)=NC=C1C(O)=O)=O)N(CC(C1)=C2OC3=C1C=CC=C3Cl)C2=O Chemical compound CC(C)C[C@@H](C(NC(C=C1)=NC=C1C(O)=O)=O)N(CC(C1)=C2OC3=C1C=CC=C3Cl)C2=O REHAXDQHKSUAPJ-KRWDZBQOSA-N 0.000 claims description 3
• FEEMKWUYTNOQCV-FQEVSTJZSA-N COC1=CC=CC2=C1CC(CN([C@@H](CC1CCCCC1)C(NC(C=C1)=NC=C1C(O)=O)=O)C1=O)=C1O2 Chemical compound COC1=CC=CC2=C1CC(CN([C@@H](CC1CCCCC1)C(NC(C=C1)=NC=C1C(O)=O)=O)C1=O)=C1O2 FEEMKWUYTNOQCV-FQEVSTJZSA-N 0.000 claims description 3
• 230000003213 activating effect Effects 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
• GXNPIVLAMAOIGX-HNNXBMFYSA-N (2s)-2-(8-chloro-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-4-methyl-n-(1,3-thiazol-2-yl)pentanamide Chemical compound O=C([C@@H](N1C(C2=C(CC3=C(Cl)C=CC=C3O2)C1)=O)CC(C)C)NC1=NC=CS1 GXNPIVLAMAOIGX-HNNXBMFYSA-N 0.000 claims description 2
• 125000004429 atom Chemical group 0.000 claims description 2
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 2
• 125000006413 ring segment Chemical group 0.000 claims 2
• 230000003993 interaction Effects 0.000 claims 1
• JSPLKZUTYZBBKA-UHFFFAOYSA-N trioxidane Chemical class OOO JSPLKZUTYZBBKA-UHFFFAOYSA-N 0.000 claims 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 10
• 230000000694 effects Effects 0.000 abstract description 7
• 239000000126 substance Substances 0.000 abstract description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract description 2
• 239000008194 pharmaceutical composition Substances 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 195
• 239000011541 reaction mixture Substances 0.000 description 84
• 239000000243 solution Substances 0.000 description 79
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 67
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
• 239000003480 eluent Substances 0.000 description 47
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 45
• 239000012044 organic layer Substances 0.000 description 45
• 238000003818 flash chromatography Methods 0.000 description 44
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
• 239000002244 precipitate Substances 0.000 description 40
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 35
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 33
• 238000006243 chemical reaction Methods 0.000 description 33
• 239000000741 silica gel Substances 0.000 description 31
• 229910002027 silica gel Inorganic materials 0.000 description 31
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 30
• 125000003118 aryl group Chemical group 0.000 description 29
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 21
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
• 150000001298 alcohols Chemical group 0.000 description 20
• 150000001299 aldehydes Chemical class 0.000 description 20
• 229940024606 amino acid Drugs 0.000 description 20
• 235000001014 amino acid Nutrition 0.000 description 20
• 239000012267 brine Substances 0.000 description 20
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 19
• 150000001413 amino acids Chemical class 0.000 description 19
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 18
• 239000000460 chlorine Substances 0.000 description 18
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 17
• 239000002253 acid Substances 0.000 description 16
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 16
• 230000007935 neutral effect Effects 0.000 description 16
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• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 14
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• 125000001424 substituent group Chemical group 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 13
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 12
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 12
• RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 11
• 125000004432 carbon atom Chemical group C* 0.000 description 11
• 239000010410 layer Substances 0.000 description 11
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• 238000004587 chromatography analysis Methods 0.000 description 10
• 239000008103 glucose Substances 0.000 description 10
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• 239000003153 chemical reaction reagent Substances 0.000 description 9
• 239000003208 petroleum Substances 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
• 150000007513 acids Chemical class 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 8
• 239000002808 molecular sieve Substances 0.000 description 8
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• BHRYBJMEVXYODE-UHFFFAOYSA-N ethyl 3-(bromomethyl)-2h-chromene-2-carboxylate Chemical compound C1=CC=C2C=C(CBr)C(C(=O)OCC)OC2=C1 BHRYBJMEVXYODE-UHFFFAOYSA-N 0.000 description 2
• PEVKVKTWYNOHLS-UHFFFAOYSA-N ethyl 3-formyl-2h-chromene-2-carboxylate Chemical compound C1=CC=C2C=C(C=O)C(C(=O)OCC)OC2=C1 PEVKVKTWYNOHLS-UHFFFAOYSA-N 0.000 description 2
• VHPFVGPRWCGGAY-UHFFFAOYSA-N ethyl 3-formyl-5-methoxy-2h-chromene-2-carboxylate Chemical compound C1=CC(OC)=C2C=C(C=O)C(C(=O)OCC)OC2=C1 VHPFVGPRWCGGAY-UHFFFAOYSA-N 0.000 description 2
• OQIVZTSICVEVIA-ZQRQZVKFSA-N ethyl 5-chloro-3-[[[(2s)-3-cyclohexyl-1-methoxy-1-oxopropan-2-yl]amino]methyl]-2h-chromene-2-carboxylate Chemical compound C([C@H](NCC1=CC2=C(Cl)C=CC=C2OC1C(=O)OCC)C(=O)OC)C1CCCCC1 OQIVZTSICVEVIA-ZQRQZVKFSA-N 0.000 description 2
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• ZRIJCJGLEFAILM-AWEZNQCLSA-N methyl (2s)-2-(5-chloro-3-oxo-1,9-dihydrochromeno[2,3-c]pyrrol-2-yl)-4-methylpentanoate Chemical compound C1=CC=C2CC(CN(C3=O)[C@@H](CC(C)C)C(=O)OC)=C3OC2=C1Cl ZRIJCJGLEFAILM-AWEZNQCLSA-N 0.000 description 2
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