CA2693820A1 - 2-aza-bicyclo[3.3.0]octane derivatives - Google Patents

Info

Publication number

CA2693820A1

CA2693820A1 CA2693820A CA2693820A CA2693820A1 CA 2693820 A1 CA2693820 A1 CA 2693820A1 CA 2693820 A CA2693820 A CA 2693820A CA 2693820 A CA2693820 A CA 2693820A CA 2693820 A1 CA2693820 A1 CA 2693820A1

Authority

CA

Canada

Prior art keywords

thiazole

carboxylic acid

methyl

phenyl

octane

Prior art date

2007-07-27

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• ADKDJHASTPQGEO-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[b]pyrrole Chemical class C1CNC2CCCC21 ADKDJHASTPQGEO-UHFFFAOYSA-N 0.000 title abstract description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 57
• 150000003839 salts Chemical class 0.000 claims abstract description 22
• 239000003814 drug Substances 0.000 claims abstract description 12
• 125000001424 substituent group Chemical group 0.000 claims description 55
• 125000000623 heterocyclic group Chemical group 0.000 claims description 34
• 229910052736 halogen Inorganic materials 0.000 claims description 32
• 150000002367 halogens Chemical class 0.000 claims description 32
• 125000003118 aryl group Chemical group 0.000 claims description 30
• -1 imidazo[2,1-b]thiazolyl Chemical group 0.000 claims description 30
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 26
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
• 238000002360 preparation method Methods 0.000 claims description 13
• 239000000460 chlorine Substances 0.000 claims description 12
• 229910052739 hydrogen Inorganic materials 0.000 claims description 12
• 239000001257 hydrogen Substances 0.000 claims description 12
• 208000020016 psychiatric disease Diseases 0.000 claims description 12
• 229910052801 chlorine Inorganic materials 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 10
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
• 125000006193 alkinyl group Chemical group 0.000 claims description 9
• 208000019116 sleep disease Diseases 0.000 claims description 9
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
• 208000012902 Nervous system disease Diseases 0.000 claims description 8
• 239000011737 fluorine Substances 0.000 claims description 8
• 229910052731 fluorine Inorganic materials 0.000 claims description 8
• 230000002265 prevention Effects 0.000 claims description 8
• 208000011117 substance-related disease Diseases 0.000 claims description 8
• 208000011580 syndromic disease Diseases 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 208000010877 cognitive disease Diseases 0.000 claims description 7
• 230000035622 drinking Effects 0.000 claims description 6
• 201000009032 substance abuse Diseases 0.000 claims description 6
• 125000000335 thiazolyl group Chemical group 0.000 claims description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 125000000597 dioxinyl group Chemical group 0.000 claims description 4
• 235000005686 eating Nutrition 0.000 claims description 4
• 125000002971 oxazolyl group Chemical group 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims description 2
• MHVSOGIDKPXDDB-ONTIZHBOSA-N n-[[(2s,3as,6as)-1-(2-cyclopropyl-5-phenyl-1,3-thiazole-4-carbonyl)-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-1,2-benzoxazole-3-carboxamide Chemical compound N1([C@H]2CCC[C@H]2C[C@H]1CNC(=O)C=1C2=CC=CC=C2ON=1)C(=O)C=1N=C(C2CC2)SC=1C1=CC=CC=C1 MHVSOGIDKPXDDB-ONTIZHBOSA-N 0.000 claims description 2
• OTTMEKXDJSZAIX-HFMPRLQTSA-N n-[[(2s,3as,6as)-1-(2-cyclopropyl-5-phenyl-1,3-thiazole-4-carbonyl)-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound N1([C@H]2CCC[C@H]2C[C@H]1CNC(=O)C=1C=2CCOC=2C=CC=1)C(=O)C=1N=C(C2CC2)SC=1C1=CC=CC=C1 OTTMEKXDJSZAIX-HFMPRLQTSA-N 0.000 claims description 2
• IHFMBXBZXXTVQP-JTAQYXEDSA-N n-[[(2s,3as,6as)-1-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=CC=C1 IHFMBXBZXXTVQP-JTAQYXEDSA-N 0.000 claims description 2
• OJJOZHOOORWXLU-FHWLQOOXSA-N n-[[(2s,3as,6as)-1-[2-amino-5-(4-methylphenyl)-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-6-methylimidazo[2,1-b][1,3]thiazole-5-carboxamide Chemical compound N1([C@H]2CCC[C@H]2C[C@H]1CNC(=O)C=1N2C=CSC2=NC=1C)C(=O)C=1N=C(N)SC=1C1=CC=C(C)C=C1 OJJOZHOOORWXLU-FHWLQOOXSA-N 0.000 claims description 2
• BYQISEBZCATOTP-JBACZVJFSA-N n-[[(2s,3as,6as)-1-[2-cyclopropyl-5-(4-fluorophenyl)-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-6-methylimidazo[2,1-b][1,3]thiazole-5-carboxamide Chemical compound N1([C@H]2CCC[C@H]2C[C@H]1CNC(=O)C=1N2C=CSC2=NC=1C)C(=O)C=1N=C(C2CC2)SC=1C1=CC=C(F)C=C1 BYQISEBZCATOTP-JBACZVJFSA-N 0.000 claims description 2
• MKOOSJHWTKSGGN-YYWHXJBOSA-N n-[[(2s,3as,6as)-1-[2-cyclopropyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-6-methylimidazo[2,1-b][1,3]thiazole-5-carboxamide Chemical compound N1([C@H]2CCC[C@H]2C[C@H]1CNC(=O)C=1N2C=CSC2=NC=1C)C(=O)C=1N=C(C2CC2)SC=1C1=CC=CC(C(F)(F)F)=C1 MKOOSJHWTKSGGN-YYWHXJBOSA-N 0.000 claims description 2
• XKTNIQYJNLZQST-PTLVVNQVSA-N n-[[(2s,3as,6as)-1-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=CC(C)=C1 XKTNIQYJNLZQST-PTLVVNQVSA-N 0.000 claims description 2
• IEPRJAMZQWKVIP-ACRUOGEOSA-N n-[[(2s,3as,6as)-1-[2-methyl-5-(4-methylphenyl)-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-6-methylimidazo[2,1-b][1,3]thiazole-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2N3C=CSC3=NC=2C)=C1C1=CC=C(C)C=C1 IEPRJAMZQWKVIP-ACRUOGEOSA-N 0.000 claims description 2
• UOGOAQDNTHKHQE-NYDSKATKSA-N n-[[(2s,3as,6as)-1-[2-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=CC(C(F)(F)F)=C1 UOGOAQDNTHKHQE-NYDSKATKSA-N 0.000 claims description 2
• YJMDFQCAHZMFGN-WATLYSKOSA-N n-[[(2s,3as,6as)-1-[5-(2,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=C(C)C=C1C YJMDFQCAHZMFGN-WATLYSKOSA-N 0.000 claims description 2
• NLZYZGYKMSDBCX-CEXJFXJFSA-N n-[[(2s,3as,6as)-1-[5-(3,4-dichlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=C(Cl)C(Cl)=C1 NLZYZGYKMSDBCX-CEXJFXJFSA-N 0.000 claims description 2
• XMHDECCCYKDFFL-CEXJFXJFSA-N n-[[(2s,3as,6as)-1-[5-(3,4-difluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=C(F)C(F)=C1 XMHDECCCYKDFFL-CEXJFXJFSA-N 0.000 claims description 2
• RVNJNVQNALAQCV-XTJBDQBJSA-N n-[[(2s,3as,6as)-1-[5-(3,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=C(C)C(C)=C1 RVNJNVQNALAQCV-XTJBDQBJSA-N 0.000 claims description 2
• VVVNENZVTHCPBD-XTJBDQBJSA-N n-[[(2s,3as,6as)-1-[5-(3,5-dimethylphenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC(C)=CC(C)=C1 VVVNENZVTHCPBD-XTJBDQBJSA-N 0.000 claims description 2
• AAKPRGKQSXOYMF-JTJYXVOQSA-N n-[[(2s,3as,6as)-1-[5-(3-acetamidophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound CC(=O)NC1=CC=CC(C2=C(N=C(C)S2)C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1 AAKPRGKQSXOYMF-JTJYXVOQSA-N 0.000 claims description 2
• WSKYKBBQUQDPAU-CEXJFXJFSA-N n-[[(2s,3as,6as)-1-[5-(3-bromo-4-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=C(F)C(Br)=C1 WSKYKBBQUQDPAU-CEXJFXJFSA-N 0.000 claims description 2
• DOTCHYMEKCDVKK-LRQRDZAKSA-N n-[[(2s,3as,6as)-1-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-1,2-benzoxazole-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C3=CC=CC=C3ON=2)=C1C1=CC=CC(Cl)=C1 DOTCHYMEKCDVKK-LRQRDZAKSA-N 0.000 claims description 2
• COJJWPSZHRAIPC-NYDSKATKSA-N n-[[(2s,3as,6as)-1-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=CC(Cl)=C1 COJJWPSZHRAIPC-NYDSKATKSA-N 0.000 claims description 2
• TYJSGGWMHHXTRT-VDGAXYAQSA-N n-[[(2s,3as,6as)-1-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-6-methylimidazo[2,1-b][1,3]thiazole-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2N3C=CSC3=NC=2C)=C1C1=CC=CC(Cl)=C1 TYJSGGWMHHXTRT-VDGAXYAQSA-N 0.000 claims description 2
• GBOFRAOTAREROM-LRQRDZAKSA-N n-[[(2s,3as,6as)-1-[5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-1,2-benzoxazole-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C3=CC=CC=C3ON=2)=C1C1=CC=CC(F)=C1 GBOFRAOTAREROM-LRQRDZAKSA-N 0.000 claims description 2
• KCNYWMNZHUVRLE-NYDSKATKSA-N n-[[(2s,3as,6as)-1-[5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=CC(F)=C1 KCNYWMNZHUVRLE-NYDSKATKSA-N 0.000 claims description 2
• UWZLSALRXPTWMD-VDGAXYAQSA-N n-[[(2s,3as,6as)-1-[5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-6-methylimidazo[2,1-b][1,3]thiazole-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2N3C=CSC3=NC=2C)=C1C1=CC=CC(F)=C1 UWZLSALRXPTWMD-VDGAXYAQSA-N 0.000 claims description 2
• HDSGIWRRXTZDIQ-LEDOBFOHSA-N n-[[(2s,3as,6as)-1-[5-(4-bromophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=C(Br)C=C1 HDSGIWRRXTZDIQ-LEDOBFOHSA-N 0.000 claims description 2
• JDOFJJCZRDUQQF-LEDOBFOHSA-N n-[[(2s,3as,6as)-1-[5-(4-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=C(F)C=C1 JDOFJJCZRDUQQF-LEDOBFOHSA-N 0.000 claims description 2
• WXNQUUOIXDSYPW-IHPCNDPISA-N n-[[(2s,3as,6as)-1-[5-(4-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-6-methylimidazo[2,1-b][1,3]thiazole-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2N3C=CSC3=NC=2C)=C1C1=CC=C(F)C=C1 WXNQUUOIXDSYPW-IHPCNDPISA-N 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 229940123730 Orexin receptor antagonist Drugs 0.000 abstract description 4
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 58
• 238000006243 chemical reaction Methods 0.000 description 56
• 125000000217 alkyl group Chemical group 0.000 description 44
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
• 230000015572 biosynthetic process Effects 0.000 description 34
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
• 238000003786 synthesis reaction Methods 0.000 description 32
• 239000000203 mixture Substances 0.000 description 29
• 239000000243 solution Substances 0.000 description 29
• 238000007127 saponification reaction Methods 0.000 description 27
• 125000003545 alkoxy group Chemical group 0.000 description 23
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
• 239000010410 layer Substances 0.000 description 21
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 19
• DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 18
• 238000000034 method Methods 0.000 description 17
• HKMLRUAPIDAGIE-UHFFFAOYSA-N methyl 2,2-dichloroacetate Chemical compound COC(=O)C(Cl)Cl HKMLRUAPIDAGIE-UHFFFAOYSA-N 0.000 description 17
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
• 239000002904 solvent Substances 0.000 description 17
• CHDSHBWEGSCEDX-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1CCO2 CHDSHBWEGSCEDX-UHFFFAOYSA-N 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
• 235000019439 ethyl acetate Nutrition 0.000 description 16
• YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 16
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
• 239000012044 organic layer Substances 0.000 description 15
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• 230000037361 pathway Effects 0.000 description 13
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
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• WSDVMICATORZTN-UHFFFAOYSA-N methyl 3-chloro-3-(2,4-dimethylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(C)C=C1C WSDVMICATORZTN-UHFFFAOYSA-N 0.000 description 2
• ATDPEFWPMHGKGM-UHFFFAOYSA-N methyl 3-chloro-3-(3,4-dichlorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(Cl)C(Cl)=C1 ATDPEFWPMHGKGM-UHFFFAOYSA-N 0.000 description 2
• GCELVOMABNBSJG-UHFFFAOYSA-N methyl 3-chloro-3-(3,4-difluorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(F)C(F)=C1 GCELVOMABNBSJG-UHFFFAOYSA-N 0.000 description 2
• SRQLCRLPEMBIIH-UHFFFAOYSA-N methyl 3-chloro-3-(3,4-dimethylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(C)C(C)=C1 SRQLCRLPEMBIIH-UHFFFAOYSA-N 0.000 description 2
• IZOJNEZHOQKSKC-UHFFFAOYSA-N methyl 3-chloro-3-(3,5-dimethylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC(C)=CC(C)=C1 IZOJNEZHOQKSKC-UHFFFAOYSA-N 0.000 description 2
• QNFXEECTBCIMFP-UHFFFAOYSA-N methyl 3-chloro-3-(3-chlorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC(Cl)=C1 QNFXEECTBCIMFP-UHFFFAOYSA-N 0.000 description 2
• ZFDZEKPSKRJHJK-UHFFFAOYSA-N methyl 3-chloro-3-(3-fluorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC(F)=C1 ZFDZEKPSKRJHJK-UHFFFAOYSA-N 0.000 description 2
• DNTLNDGNTHOJIZ-UHFFFAOYSA-N methyl 3-chloro-3-(3-methylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC(C)=C1 DNTLNDGNTHOJIZ-UHFFFAOYSA-N 0.000 description 2
• QFZGJNRSDDUIIV-UHFFFAOYSA-N methyl 3-chloro-3-(3-nitrophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC([N+]([O-])=O)=C1 QFZGJNRSDDUIIV-UHFFFAOYSA-N 0.000 description 2
• KZOXLFIUUVATMN-UHFFFAOYSA-N methyl 5-(2,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C(=CC(C)=CC=2)C)=C1C(=O)OC KZOXLFIUUVATMN-UHFFFAOYSA-N 0.000 description 2
• YGTYCVKLOJHTEU-UHFFFAOYSA-N methyl 5-(3,4-dichlorophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(Cl)C(Cl)=CC=2)=C1C(=O)OC YGTYCVKLOJHTEU-UHFFFAOYSA-N 0.000 description 2
• XCXIVLCMRKWWQY-UHFFFAOYSA-N methyl 5-(3,4-difluorophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(F)C(F)=CC=2)=C1C(=O)OC XCXIVLCMRKWWQY-UHFFFAOYSA-N 0.000 description 2
• UTLYGYNJWOAWHK-UHFFFAOYSA-N methyl 5-(3,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(C)C(C)=CC=2)=C1C(=O)OC UTLYGYNJWOAWHK-UHFFFAOYSA-N 0.000 description 2
• NRGLPUBJIJZGIG-UHFFFAOYSA-N methyl 5-(3,5-dimethylphenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(C)C=C(C)C=2)=C1C(=O)OC NRGLPUBJIJZGIG-UHFFFAOYSA-N 0.000 description 2
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