JP2007510629A - 新規ｍｃｈ受容体アンタゴニスト - Google Patents

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Publication number

JP2007510629A

JP2007510629A JP2006536645A JP2006536645A JP2007510629A JP 2007510629 A JP2007510629 A JP 2007510629A JP 2006536645 A JP2006536645 A JP 2006536645A JP 2006536645 A JP2006536645 A JP 2006536645A JP 2007510629 A JP2007510629 A JP 2007510629A

Authority

JP

Japan

Prior art keywords

alkyl

phenoxy

oxadiazol

group

ethylsulfanylmethyl

Prior art date

2003-10-22

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.)

Pending

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• Espacenet
• Global Dossier
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• 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 title description 3
• 102000006953 melanin-concentrating hormone receptor activity proteins Human genes 0.000 title 1
• 239000002464 receptor antagonist Substances 0.000 title 1
• 229940044551 receptor antagonist Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 150
• 208000008589 Obesity Diseases 0.000 claims abstract description 20
• 235000020824 obesity Nutrition 0.000 claims abstract description 20
• 150000003839 salts Chemical class 0.000 claims abstract description 18
• 238000011282 treatment Methods 0.000 claims abstract description 17
• 101800002739 Melanin-concentrating hormone Proteins 0.000 claims abstract description 14
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 5
• 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 claims abstract description 4
• 102000047659 melanin-concentrating hormone Human genes 0.000 claims abstract description 4
• -1 —O-aryl Chemical group 0.000 claims description 117
• 238000000034 method Methods 0.000 claims description 85
• 125000000217 alkyl group Chemical group 0.000 claims description 51
• 239000000203 mixture Substances 0.000 claims description 49
• 125000003118 aryl group Chemical group 0.000 claims description 46
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
• 125000000623 heterocyclic group Chemical group 0.000 claims description 22
• 125000005647 linker group Chemical group 0.000 claims description 21
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 19
• 125000005843 halogen group Chemical group 0.000 claims description 19
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 17
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 16
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
• 239000001257 hydrogen Substances 0.000 claims description 15
• 229910052739 hydrogen Inorganic materials 0.000 claims description 15
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 14
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 14
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 13
• 229910052757 nitrogen Inorganic materials 0.000 claims description 13
• 201000010099 disease Diseases 0.000 claims description 12
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 10
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
• 125000001188 haloalkyl group Chemical group 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 10
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
• 239000001301 oxygen Substances 0.000 claims description 9
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 8
• 125000003545 alkoxy group Chemical group 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000001624 naphthyl group Chemical group 0.000 claims description 8
• 125000004043 oxo group Chemical group O=* 0.000 claims description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 7
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
• 125000004122 cyclic group Chemical group 0.000 claims description 7
• MVWGDEIHAMVCEQ-UHFFFAOYSA-N n,n-dimethyl-1-[1-methylsulfonyl-6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]indol-2-yl]methanamine Chemical compound C1=C2N(S(C)(=O)=O)C(CN(C)C)=CC2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 MVWGDEIHAMVCEQ-UHFFFAOYSA-N 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• ROYQQLMXAJXHOL-UHFFFAOYSA-N 5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-2-(2-piperidin-1-ylethyl)-3h-isoindol-1-one Chemical compound C1C2=CC(C=3OC(CSCCOC=4C=CC=CC=4)=NN=3)=CC=C2C(=O)N1CCN1CCCCC1 ROYQQLMXAJXHOL-UHFFFAOYSA-N 0.000 claims description 6
• 125000003342 alkenyl group Chemical group 0.000 claims description 6
• 125000004429 atom Chemical group 0.000 claims description 6
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 6
• 229910052799 carbon Inorganic materials 0.000 claims description 6
• 229910052717 sulfur Chemical group 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• FGDTVLQNKWSOJO-UHFFFAOYSA-N n,n-dimethyl-1-[1-methylsulfonyl-5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]indol-2-yl]methanamine Chemical compound C=1C=C2N(S(C)(=O)=O)C(CN(C)C)=CC2=CC=1C(O1)=NN=C1CSCCOC1=CC=CC=C1 FGDTVLQNKWSOJO-UHFFFAOYSA-N 0.000 claims description 5
• 239000012453 solvate Substances 0.000 claims description 5
• KGFUPXNXKMTREV-BTJKTKAUSA-N (z)-but-2-enedioic acid;n,n-dimethyl-1-[6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1h-indol-3-yl]methanamine Chemical compound OC(=O)\C=C/C(O)=O.C=1C=C2C(CN(C)C)=CNC2=CC=1C(O1)=NN=C1CSCCOC1=CC=CC=C1 KGFUPXNXKMTREV-BTJKTKAUSA-N 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 4
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• GTGMJBRHGYLFMK-UHFFFAOYSA-N n,n-dimethyl-1-[5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1-benzofuran-2-yl]methanamine;oxalic acid Chemical compound OC(=O)C(O)=O.C=1C=C2OC(CN(C)C)=CC2=CC=1C(O1)=NN=C1CSCCOC1=CC=CC=C1 GTGMJBRHGYLFMK-UHFFFAOYSA-N 0.000 claims description 4
• MEQGXPXYVTZVHQ-UHFFFAOYSA-N n,n-dimethyl-1-[6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1h-indol-2-yl]methanamine Chemical compound C1=C2NC(CN(C)C)=CC2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 MEQGXPXYVTZVHQ-UHFFFAOYSA-N 0.000 claims description 4
• CRPQTFQASNDDOH-UHFFFAOYSA-N n,n-dimethyl-1-[6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]naphthalen-2-yl]methanamine Chemical compound C1=CC2=CC(CN(C)C)=CC=C2C=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 CRPQTFQASNDDOH-UHFFFAOYSA-N 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
• 239000011593 sulfur Chemical group 0.000 claims description 4
• FWMVAFWOQYSPSU-ODZAUARKSA-N C(\C=C/C(=O)O)(=O)O.O1N=NC=C1 Chemical compound C(\C=C/C(=O)O)(=O)O.O1N=NC=C1 FWMVAFWOQYSPSU-ODZAUARKSA-N 0.000 claims description 3
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
• 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 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• FVZSEZORVQWGNL-UHFFFAOYSA-N n,n-dimethyl-1-[1-methyl-5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]indol-3-yl]methanamine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C2C(CN(C)C)=CN(C)C2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 FVZSEZORVQWGNL-UHFFFAOYSA-N 0.000 claims description 3
• UWTZXSGHOKFTGN-UHFFFAOYSA-N n,n-dimethyl-1-[1-methyl-6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]indol-2-yl]methanamine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C2N(C)C(CN(C)C)=CC2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 UWTZXSGHOKFTGN-UHFFFAOYSA-N 0.000 claims description 3
• CZUYHBPJKIDCQA-UHFFFAOYSA-N n,n-dimethyl-1-[5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1h-indol-3-yl]methanamine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C2C(CN(C)C)=CNC2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 CZUYHBPJKIDCQA-UHFFFAOYSA-N 0.000 claims description 3
• KXXVTHPNMUULHT-UHFFFAOYSA-N n,n-dimethyl-1-[6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1-benzofuran-2-yl]methanamine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C2OC(CN(C)C)=CC2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 KXXVTHPNMUULHT-UHFFFAOYSA-N 0.000 claims description 3
• ZUYUUAIKJFTKND-UHFFFAOYSA-N n,n-dimethyl-4-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]naphthalen-1-amine Chemical compound C12=CC=CC=C2C(N(C)C)=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 ZUYUUAIKJFTKND-UHFFFAOYSA-N 0.000 claims description 3
• 229920006395 saturated elastomer Polymers 0.000 claims description 3
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 3
• 125000002947 alkylene group Chemical group 0.000 claims description 2
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 2
• 125000005518 carboxamido group Chemical group 0.000 claims description 2
• 125000001072 heteroaryl group Chemical group 0.000 claims description 2
• 230000002401 inhibitory effect Effects 0.000 claims description 2
• VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 2
• 239000000651 prodrug Substances 0.000 claims description 2
• 229940002612 prodrug Drugs 0.000 claims description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
• IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims 2
• BDJAEZRIGNCQBZ-UHFFFAOYSA-N methylcyclobutane Chemical compound CC1CCC1 BDJAEZRIGNCQBZ-UHFFFAOYSA-N 0.000 claims 2
• UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 claims 2
• GDOPTJXRTPNYNR-UHFFFAOYSA-N methylcyclopentane Chemical compound CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 claims 2
• 125000002393 azetidinyl group Chemical group 0.000 claims 1
• PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 claims 1
• GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 claims 1
• VNXBKJFUJUWOCW-UHFFFAOYSA-N methylcyclopropane Chemical compound CC1CC1 VNXBKJFUJUWOCW-UHFFFAOYSA-N 0.000 claims 1
• QMZSETBPQAVBMN-UHFFFAOYSA-N n,n-dimethyl-1-[5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1h-indol-2-yl]methanamine Chemical compound C=1C=C2NC(CN(C)C)=CC2=CC=1C(O1)=NN=C1CSCCOC1=CC=CC=C1 QMZSETBPQAVBMN-UHFFFAOYSA-N 0.000 claims 1
• 239000000825 pharmaceutical preparation Substances 0.000 claims 1
• 125000003386 piperidinyl group Chemical group 0.000 claims 1
• 239000003667 hormone antagonist Substances 0.000 abstract description 2
• 238000006243 chemical reaction Methods 0.000 description 95
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 74
• 239000000243 solution Substances 0.000 description 70
• 238000010168 coupling process Methods 0.000 description 64
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
• 239000007787 solid Substances 0.000 description 51
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 47
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 46
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
• 239000002904 solvent Substances 0.000 description 46
• 238000005859 coupling reaction Methods 0.000 description 44
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• 238000004587 chromatography analysis Methods 0.000 description 34
• 230000008878 coupling Effects 0.000 description 34
• 238000007429 general method Methods 0.000 description 34
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 33
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
• 239000003921 oil Substances 0.000 description 30
• 235000019198 oils Nutrition 0.000 description 30
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
• 238000004458 analytical method Methods 0.000 description 26
• 235000019439 ethyl acetate Nutrition 0.000 description 26
• 239000002585 base Substances 0.000 description 25
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 24
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 24
• 238000002360 preparation method Methods 0.000 description 24
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 22
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
• 230000015572 biosynthetic process Effects 0.000 description 20
• 239000012442 inert solvent Substances 0.000 description 20
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 18
• 235000019502 Orange oil Nutrition 0.000 description 17
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 17
• 239000003795 chemical substances by application Substances 0.000 description 17
• 239000010502 orange oil Substances 0.000 description 17
• 239000012044 organic layer Substances 0.000 description 17
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 16
• 230000010933 acylation Effects 0.000 description 16
• 238000005917 acylation reaction Methods 0.000 description 16
• 150000001412 amines Chemical class 0.000 description 15
• 238000005755 formation reaction Methods 0.000 description 13
• 125000002524 organometallic group Chemical group 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• 238000005694 sulfonylation reaction Methods 0.000 description 13
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• 230000006103 sulfonylation Effects 0.000 description 12
• 239000004202 carbamide Substances 0.000 description 11
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
• 102400001132 Melanin-concentrating hormone Human genes 0.000 description 10
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
• 238000005804 alkylation reaction Methods 0.000 description 10
• 239000012267 brine Substances 0.000 description 10
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
• 239000003054 catalyst Substances 0.000 description 10
• 239000003153 chemical reaction reagent Substances 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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