KR100447000B1 - 엔도텔린길항제 - Google Patents

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Publication number

KR100447000B1

KR100447000B1 KR1019970701079A KR19970701079A KR100447000B1 KR 100447000 B1 KR100447000 B1 KR 100447000B1 KR 1019970701079 A KR1019970701079 A KR 1019970701079A KR 19970701079 A KR19970701079 A KR 19970701079A KR 100447000 B1 KR100447000 B1 KR 100447000B1

Authority

KR

South Korea

Prior art keywords

trans

carboxylic acid

methoxyphenyl

benzodioxol

pyrrolidine

Prior art date

1994-08-19

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.)

Expired - Lifetime

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• 108050009340 Endothelin Proteins 0.000 title abstract description 23
• 102000002045 Endothelin Human genes 0.000 title abstract description 23
• ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 title abstract description 22
• 239000005557 antagonist Substances 0.000 title abstract description 8
• 150000003839 salts Chemical class 0.000 claims abstract description 32
• -1 4-fluor Lophenyl Chemical group 0.000 claims description 582
• 150000001875 compounds Chemical class 0.000 claims description 483
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 224
• 239000002253 acid Substances 0.000 claims description 71
• 125000000217 alkyl group Chemical group 0.000 claims description 69
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 69
• JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 claims description 67
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
• 125000003118 aryl group Chemical group 0.000 claims description 43
• 125000000623 heterocyclic group Chemical group 0.000 claims description 38
• 125000002947 alkylene group Chemical group 0.000 claims description 36
• 239000001257 hydrogen Substances 0.000 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 35
• 229910052757 nitrogen Inorganic materials 0.000 claims description 34
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
• 125000001424 substituent group Chemical group 0.000 claims description 27
• 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 26
• 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 26
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 14
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
• 125000004212 difluorophenyl group Chemical group 0.000 claims description 14
• 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 14
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 14
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 13
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 13
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 12
• 125000004076 pyridyl group Chemical group 0.000 claims description 12
• 125000005843 halogen group Chemical group 0.000 claims description 11
• 125000002541 furyl group Chemical group 0.000 claims description 10
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
• 201000001320 Atherosclerosis Diseases 0.000 claims description 6
• UBAJKIWNMWBZPZ-RBBKRZOGSA-N COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CC(=O)N(CC(C)C)C Chemical compound COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CC(=O)N(CC(C)C)C UBAJKIWNMWBZPZ-RBBKRZOGSA-N 0.000 claims description 6
• 125000004104 aryloxy group Chemical group 0.000 claims description 6
• MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 claims description 6
• FQGXQQWFNOVDHE-XUZZJYLKSA-N COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CC(=O)N(C1CCCCC1)C Chemical compound COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CC(=O)N(C1CCCCC1)C FQGXQQWFNOVDHE-XUZZJYLKSA-N 0.000 claims description 5
• 125000001624 naphthyl group Chemical group 0.000 claims description 5
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 5
• ZSDIDUYODFAJRX-WTEXUFCASA-N (3S,4R)-2,4-bis(1,3-benzodioxol-5-yl)-1-(dibutylcarbamoyl)-2-methylpyrrolidine-3-carboxylic acid Chemical compound C(CCC)N(C(=O)N1C([C@H]([C@@H](C1)C1=CC2=C(OCO2)C=C1)C(=O)O)(C1=CC2=C(OCO2)C=C1)C)CCCC ZSDIDUYODFAJRX-WTEXUFCASA-N 0.000 claims description 4
• AKFPXVDFBYGECM-JHEWSRJYSA-N (3s,4r)-2-[2-(dibutylamino)-2-oxoethyl]-4-(4-fluorophenyl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid Chemical compound C1([C@@H]2CNC([C@H]2C(O)=O)(CC(=O)N(CCCC)CCCC)C=2C=CC(OC)=CC=2)=CC=C(F)C=C1 AKFPXVDFBYGECM-JHEWSRJYSA-N 0.000 claims description 4
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
• TXFRRALZVDDRIU-AHKZPQOWSA-N COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CCN(C(C1=CC=CC=C1)=O)CCC Chemical compound COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CCN(C(C1=CC=CC=C1)=O)CCC TXFRRALZVDDRIU-AHKZPQOWSA-N 0.000 claims description 4
• FHMHKCBLGROSFC-VBSCFIAOSA-N COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)C\C=C\CC(C)C Chemical compound COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)C\C=C\CC(C)C FHMHKCBLGROSFC-VBSCFIAOSA-N 0.000 claims description 4
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
• WNAIAQMVMMTZPO-UHFFFAOYSA-N Cl.N1CC(C=2C=C3OCOC3=CC=2)C(C(O)=O)C1(CC(=O)N(CCCC)CCCC)C1=CC=C(O)C=C1 Chemical compound Cl.N1CC(C=2C=C3OCOC3=CC=2)C(C(O)=O)C1(CC(=O)N(CCCC)CCCC)C1=CC=C(O)C=C1 WNAIAQMVMMTZPO-UHFFFAOYSA-N 0.000 claims description 4
• 206010019280 Heart failures Diseases 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• WDFVWPLFSJGMFD-COHKGRJRSA-N (2r,3r,4r)-4-(1,3-benzodioxol-5-yl)-1-[(2r)-1-(dipropylamino)-1-oxopentan-2-yl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid Chemical compound C1([C@H]2[C@@H]([C@@H](CN2[C@H](CCC)C(=O)N(CCC)CCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 WDFVWPLFSJGMFD-COHKGRJRSA-N 0.000 claims description 3
• WDFVWPLFSJGMFD-YFQNEARWSA-N (2s,3s,4s)-4-(1,3-benzodioxol-5-yl)-1-[(2s)-1-(dipropylamino)-1-oxopentan-2-yl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid Chemical compound C1([C@@H]2[C@H]([C@H](CN2[C@@H](CCC)C(=O)N(CCC)CCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 WDFVWPLFSJGMFD-YFQNEARWSA-N 0.000 claims description 3
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
• 201000006474 Brain Ischemia Diseases 0.000 claims description 3
• GZPGQECIBQOJOW-XZOQPEGZSA-N C(CCC)N(CCCC)C(=O)CN1[C@H](C[C@@H](C1)C1=CC2=C(OCO2)C=C1)C=1C=NC=CC1 Chemical compound C(CCC)N(CCCC)C(=O)CN1[C@H](C[C@@H](C1)C1=CC2=C(OCO2)C=C1)C=1C=NC=CC1 GZPGQECIBQOJOW-XZOQPEGZSA-N 0.000 claims description 3
• CLSCPJUKQWNXSS-LADGPHEKSA-N COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)C(=O)N(CCCC)CCCC Chemical compound COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)C(=O)N(CCCC)CCCC CLSCPJUKQWNXSS-LADGPHEKSA-N 0.000 claims description 3
• SXZRDPMVHCQDEE-GXBNZEJLSA-N COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CC(=O)N1C[C@H](C[C@@H](C1)C)C Chemical compound COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CC(=O)N1C[C@H](C[C@@H](C1)C)C SXZRDPMVHCQDEE-GXBNZEJLSA-N 0.000 claims description 3
• 206010008120 Cerebral ischaemia Diseases 0.000 claims description 3
• 206010020772 Hypertension Diseases 0.000 claims description 3
• 206010028980 Neoplasm Diseases 0.000 claims description 3
• 201000011510 cancer Diseases 0.000 claims description 3
• 206010008118 cerebral infarction Diseases 0.000 claims description 3
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
• 208000031225 myocardial ischemia Diseases 0.000 claims description 3
• 125000003386 piperidinyl group Chemical group 0.000 claims description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
• WDFVWPLFSJGMFD-ACWWYGLDSA-N (2r,3r,4r)-4-(1,3-benzodioxol-5-yl)-1-[(2s)-1-(dipropylamino)-1-oxopentan-2-yl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid Chemical compound C1([C@H]2[C@@H]([C@@H](CN2[C@@H](CCC)C(=O)N(CCC)CCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 WDFVWPLFSJGMFD-ACWWYGLDSA-N 0.000 claims description 2
• WDFVWPLFSJGMFD-KSZYUSJVSA-N (2s,3s,4s)-4-(1,3-benzodioxol-5-yl)-1-[(2r)-1-(dipropylamino)-1-oxopentan-2-yl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid Chemical compound C1([C@@H]2[C@H]([C@H](CN2[C@H](CCC)C(=O)N(CCC)CCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 WDFVWPLFSJGMFD-KSZYUSJVSA-N 0.000 claims description 2
• ZFENGFYHJVNMFK-JTHBVZDNSA-N COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CC(=O)N1CC(CCC1)(C)C Chemical compound COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CC(=O)N1CC(CCC1)(C)C ZFENGFYHJVNMFK-JTHBVZDNSA-N 0.000 claims description 2
• 206010060862 Prostate cancer Diseases 0.000 claims description 2
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
• 125000002757 morpholinyl group Chemical group 0.000 claims description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
• 208000037803 restenosis Diseases 0.000 claims description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 230000020341 sensory perception of pain Effects 0.000 claims description 2
• DQFUEDRYWCNOLS-UHFFFAOYSA-N 1-[2-(dibutylamino)-2-oxoethyl]pyrrolidine-3-carboxylic acid Chemical compound CCCCN(CCCC)C(=O)CN1CCC(C(O)=O)C1 DQFUEDRYWCNOLS-UHFFFAOYSA-N 0.000 claims 7
• 239000008194 pharmaceutical composition Substances 0.000 claims 4
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 2
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims 1
• PEIGAYQLTHRXCX-UHFFFAOYSA-N 1-[2-(butylamino)-2-oxoethyl]pyrrolidine-3-carboxylic acid Chemical compound CCCCNC(=O)CN1CCC(C(O)=O)C1 PEIGAYQLTHRXCX-UHFFFAOYSA-N 0.000 claims 1
• 206010003162 Arterial injury Diseases 0.000 claims 1
• KOIALUCHXOCQIG-RBBKRZOGSA-N COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CCN(C(=O)C(C)C)C Chemical compound COC1=CC=C(C=C1)[C@@H]1N(C[C@H](C1)C1=CC2=C(OCO2)C=C1)CCN(C(=O)C(C)C)C KOIALUCHXOCQIG-RBBKRZOGSA-N 0.000 claims 1
• CDGLZBOSGIOPII-UHFFFAOYSA-N N1CC(C=2C=C3OCOC3=CC=2)C(C(O)=O)C1(CC(=O)N(CCCC)CCCC)C1=CC=C(OCOC)C=C1 Chemical class N1CC(C=2C=C3OCOC3=CC=2)C(C(O)=O)C1(CC(=O)N(CCCC)CCCC)C1=CC=C(OCOC)C=C1 CDGLZBOSGIOPII-UHFFFAOYSA-N 0.000 claims 1
• 125000005036 alkoxyphenyl group Chemical group 0.000 claims 1
• 125000004652 decahydroisoquinolinyl group Chemical group C1(NCCC2CCCCC12)* 0.000 claims 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
• 125000006501 nitrophenyl group Chemical group 0.000 claims 1
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 261
• 239000000543 intermediate Substances 0.000 abstract description 18
• 230000008569 process Effects 0.000 abstract description 12
• 239000000243 solution Substances 0.000 description 158
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 137
• 239000000203 mixture Substances 0.000 description 137
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 136
• 239000007787 solid Substances 0.000 description 104
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 96
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 90
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 87
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 61
• SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 58
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
• 239000000047 product Substances 0.000 description 54
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 53
• 235000019439 ethyl acetate Nutrition 0.000 description 52
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 51
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 44
• 150000002148 esters Chemical class 0.000 description 41
• 230000002829 reductive effect Effects 0.000 description 41
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
• WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 38
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 37
• 239000011734 sodium Substances 0.000 description 37
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 36
• 239000000741 silica gel Substances 0.000 description 36
• 229910002027 silica gel Inorganic materials 0.000 description 36
• 238000006243 chemical reaction Methods 0.000 description 33
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 33
• 239000012043 crude product Substances 0.000 description 33
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
• 229940081310 piperonal Drugs 0.000 description 29
• 125000003545 alkoxy group Chemical group 0.000 description 28
• 229940093499 ethyl acetate Drugs 0.000 description 28
• 239000011541 reaction mixture Substances 0.000 description 27
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
• 239000012267 brine Substances 0.000 description 24
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 24
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
• 239000000460 chlorine Substances 0.000 description 23
• 239000003921 oil Substances 0.000 description 23
• 235000019198 oils Nutrition 0.000 description 23
• DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 22
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
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