CA2652385A1 - Novel mch receptor antagonists - Google Patents

Info

Publication number

CA2652385A1

CA2652385A1 CA002652385A CA2652385A CA2652385A1 CA 2652385 A1 CA2652385 A1 CA 2652385A1 CA 002652385 A CA002652385 A CA 002652385A CA 2652385 A CA2652385 A CA 2652385A CA 2652385 A1 CA2652385 A1 CA 2652385A1

Authority

CA

Canada

Prior art keywords

phenyl

methoxy

chloro

thieno

pyridin

Prior art date

2006-06-08

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

• 102000029828 Melanin-concentrating hormone receptor Human genes 0.000 title description 2
• 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 title description 2
• 229940044551 receptor antagonist Drugs 0.000 title description 2
• 239000002464 receptor antagonist Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 244
• 239000000203 mixture Substances 0.000 claims abstract description 150
• 150000003839 salts Chemical class 0.000 claims abstract description 23
• 208000008589 Obesity Diseases 0.000 claims abstract description 16
• 235000020824 obesity Nutrition 0.000 claims abstract description 16
• -1 -OR6 Chemical group 0.000 claims description 97
• 239000001257 hydrogen Substances 0.000 claims description 86
• 229910052739 hydrogen Inorganic materials 0.000 claims description 86
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 73
• 125000000623 heterocyclic group Chemical group 0.000 claims description 68
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 63
• 238000000034 method Methods 0.000 claims description 60
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 59
• 229910052757 nitrogen Inorganic materials 0.000 claims description 49
• 125000001153 fluoro group Chemical group F* 0.000 claims description 48
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 42
• 150000002431 hydrogen Chemical group 0.000 claims description 42
• 125000000217 alkyl group Chemical group 0.000 claims description 38
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 38
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 33
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 26
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 24
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 18
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
• 125000005843 halogen group Chemical group 0.000 claims description 15
• 125000004043 oxo group Chemical group O=* 0.000 claims description 15
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 15
• 125000001188 haloalkyl group Chemical group 0.000 claims description 14
• 125000004193 piperazinyl group Chemical group 0.000 claims description 14
• 125000002393 azetidinyl group Chemical group 0.000 claims description 12
• 125000003386 piperidinyl group Chemical group 0.000 claims description 12
• 125000002883 imidazolyl group Chemical group 0.000 claims description 11
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 9
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
• 125000005959 diazepanyl group Chemical group 0.000 claims description 6
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
• 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• DANNXIYTSPUKNZ-HXUWFJFHSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3r)-piperidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@@H]1CCCNC1 DANNXIYTSPUKNZ-HXUWFJFHSA-N 0.000 claims description 4
• CZRGFNLUHBYQMI-DENIHFKCSA-N 2-(4-chlorophenyl)-6-[4-[(3r,4r)-4-hydroxy-1-methylpyrrolidin-3-yl]oxy-3-methoxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@@H]1CN(C)C[C@H]1O CZRGFNLUHBYQMI-DENIHFKCSA-N 0.000 claims description 4
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
• NRPHIGGEADJUSS-LJQANCHMSA-N 2-(4-chlorophenyl)-6-[4-[(3r)-3-hydroxypyrrolidin-1-yl]-3-methoxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N1CC[C@@H](O)C1 NRPHIGGEADJUSS-LJQANCHMSA-N 0.000 claims description 3
• 239000002830 appetite depressant Substances 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 3
• MRPMZDZHOMJYJI-FQEVSTJZSA-N (5s)-5-[[4-[2-(4-chlorophenyl)-7-oxothieno[2,3-c]pyridin-6-yl]-2-methoxyphenoxy]methyl]-4-methylmorpholin-3-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OC[C@@H]1COCC(=O)N1C MRPMZDZHOMJYJI-FQEVSTJZSA-N 0.000 claims description 2
• RDXDDIURVFTSGG-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-fluoro-4-(1-methylazetidin-3-yl)oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound C1N(C)CC1OC1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1F RDXDDIURVFTSGG-UHFFFAOYSA-N 0.000 claims description 2
• RFSADOOPEMNMGH-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN1CCCC1 RFSADOOPEMNMGH-UHFFFAOYSA-N 0.000 claims description 2
• BYWIKAYNGOZCQR-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3-methylimidazol-4-yl)methoxy]phenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCC1=CN=CN1C BYWIKAYNGOZCQR-UHFFFAOYSA-N 0.000 claims description 2
• AGDPDWYQZACUSZ-OAQYLSRUSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3r)-1-methylpiperidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@@H]1CCCN(C)C1 AGDPDWYQZACUSZ-OAQYLSRUSA-N 0.000 claims description 2
• NEQYTWHZDNXZAF-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[4-(1-methylpyrrolidine-3-carbonyl)phenyl]thieno[2,3-c]pyridin-7-one Chemical compound C1N(C)CCC1C(=O)C1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1 NEQYTWHZDNXZAF-UHFFFAOYSA-N 0.000 claims description 2
• DYHPKCICOMNEHT-UHFFFAOYSA-N 2-(4-methoxyphenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=CC(OC)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C(OC)C(OCCN3CCCC3)=CC=1)CC2 DYHPKCICOMNEHT-UHFFFAOYSA-N 0.000 claims description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
• XCEICWWFGPUZHI-UHFFFAOYSA-N 6-(4-aminophenyl)-2-(4-chlorophenyl)thieno[2,3-c]pyridin-7-one Chemical compound C1=CC(N)=CC=C1N1C(=O)C(SC(=C2)C=3C=CC(Cl)=CC=3)=C2C=C1 XCEICWWFGPUZHI-UHFFFAOYSA-N 0.000 claims description 2
• NAWFRFAJOADEHA-UHFFFAOYSA-N 6-[3-methoxy-4-(2-morpholin-4-ylethoxy)phenyl]-2-(4-methoxyphenyl)-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=CC(OC)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C(OC)C(OCCN3CCOCC3)=CC=1)CC2 NAWFRFAJOADEHA-UHFFFAOYSA-N 0.000 claims description 2
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• GVZOAZDOGPCEIG-UHFFFAOYSA-N n-[4-[2-(4-chlorophenyl)-7-oxothieno[2,3-c]pyridin-6-yl]-2-methoxyphenyl]-2-pyrrolidin-1-ylacetamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1NC(=O)CN1CCCC1 GVZOAZDOGPCEIG-UHFFFAOYSA-N 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
• LCIHRXSOFXUFGE-UHFFFAOYSA-N n-[4-[2-(4-chlorophenyl)-7-oxo-4,5-dihydrothieno[2,3-c]pyridin-6-yl]-2-methoxyphenyl]-2-pyrrolidin-1-ylacetamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(Cl)=CC=2)=O)=CC=C1NC(=O)CN1CCCC1 LCIHRXSOFXUFGE-UHFFFAOYSA-N 0.000 claims 2
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
• 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims 1
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
• SKTCYPNSGXYYLI-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3CC2)C=2C(=CC(Cl)=CC=2)Cl)=O)=CC=C1OCCN1CCCC1 SKTCYPNSGXYYLI-UHFFFAOYSA-N 0.000 claims 1
• ACVJLNZNERVECQ-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-(3-fluoro-4-piperazin-1-ylphenyl)thieno[2,3-c]pyridin-7-one Chemical compound FC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N1CCNCC1 ACVJLNZNERVECQ-UHFFFAOYSA-N 0.000 claims 1
• ZMAHJOALZXKRCN-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-(3-methoxy-4-piperidin-4-yloxyphenyl)thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OC1CCNCC1 ZMAHJOALZXKRCN-UHFFFAOYSA-N 0.000 claims 1
• LIUNOICECXIDLZ-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-(1-methylazetidin-3-yl)oxyphenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OC1CN(C)C1 LIUNOICECXIDLZ-UHFFFAOYSA-N 0.000 claims 1
• PSULEVZMDDCOLR-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-(1-methylazetidin-3-yl)oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OC1CN(C)C1 PSULEVZMDDCOLR-UHFFFAOYSA-N 0.000 claims 1
• PKLDHRJOXRBRNR-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N1CCN(C)CC1 PKLDHRJOXRBRNR-UHFFFAOYSA-N 0.000 claims 1
• KUZMWADQWJCNMH-LJQANCHMSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3r)-pyrrolidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@@H]1CCNC1 KUZMWADQWJCNMH-LJQANCHMSA-N 0.000 claims 1
• AGDPDWYQZACUSZ-NRFANRHFSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3s)-1-methylpiperidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@H]1CCCN(C)C1 AGDPDWYQZACUSZ-NRFANRHFSA-N 0.000 claims 1
• QXSOSEXLDZKZSG-IBGZPJMESA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3s)-3-(methylamino)pyrrolidin-1-yl]phenyl]thieno[2,3-c]pyridin-7-one Chemical compound C1[C@@H](NC)CCN1C1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1OC QXSOSEXLDZKZSG-IBGZPJMESA-N 0.000 claims 1
• DANNXIYTSPUKNZ-FQEVSTJZSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3s)-piperidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@H]1CCCNC1 DANNXIYTSPUKNZ-FQEVSTJZSA-N 0.000 claims 1
• ARTILZSBVXIGSZ-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[4-(1-methylazetidine-3-carbonyl)phenyl]thieno[2,3-c]pyridin-7-one Chemical compound C1N(C)CC1C(=O)C1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1 ARTILZSBVXIGSZ-UHFFFAOYSA-N 0.000 claims 1
• NGSRPWCECXHPGY-OAQYLSRUSA-N 2-(4-chlorophenyl)-6-[4-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]-3-methoxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N1CC[C@@H](N(C)C)C1 NGSRPWCECXHPGY-OAQYLSRUSA-N 0.000 claims 1
• NGSRPWCECXHPGY-NRFANRHFSA-N 2-(4-chlorophenyl)-6-[4-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]-3-methoxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N1CC[C@H](N(C)C)C1 NGSRPWCECXHPGY-NRFANRHFSA-N 0.000 claims 1
• XAAKSDZMQPTDBS-UHFFFAOYSA-N 6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-2-[4-(trifluoromethyl)phenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=O)=CC=C1OCCN1CCCC1 XAAKSDZMQPTDBS-UHFFFAOYSA-N 0.000 claims 1
• 101800002739 Melanin-concentrating hormone Proteins 0.000 abstract description 22
• ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 abstract description 22
• 102000047659 melanin-concentrating hormone Human genes 0.000 abstract description 22
• 201000010099 disease Diseases 0.000 abstract description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
• 239000003667 hormone antagonist Substances 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 229
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 185
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 153
• 238000002360 preparation method Methods 0.000 description 126
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 124
• 239000012141 concentrate Substances 0.000 description 120
• 238000003756 stirring Methods 0.000 description 117
• 239000000243 solution Substances 0.000 description 114
• 235000019439 ethyl acetate Nutrition 0.000 description 103
• 229910001868 water Inorganic materials 0.000 description 100
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 88
• 238000006243 chemical reaction Methods 0.000 description 86
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 81
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 81
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 80
• 239000000284 extract Substances 0.000 description 70
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 64
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 54
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
• 239000007787 solid Substances 0.000 description 50
• 239000013058 crude material Substances 0.000 description 40
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 34
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
• 239000012044 organic layer Substances 0.000 description 33
• 239000012267 brine Substances 0.000 description 29
• 238000004587 chromatography analysis Methods 0.000 description 29
• 239000000047 product Substances 0.000 description 29
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
• 239000002904 solvent Substances 0.000 description 27
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 24
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
• 229940093499 ethyl acetate Drugs 0.000 description 23
• 238000010898 silica gel chromatography Methods 0.000 description 23
• 229910052938 sodium sulfate Inorganic materials 0.000 description 23
• 235000011152 sodium sulphate Nutrition 0.000 description 23
• 238000010791 quenching Methods 0.000 description 22
• 238000010992 reflux Methods 0.000 description 22
• 239000002002 slurry Substances 0.000 description 22
• 239000000126 substance Substances 0.000 description 22
• 239000007832 Na2SO4 Substances 0.000 description 20
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 20
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
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