JPH0213669B2 - - Google Patents
Info
- Publication number
- JPH0213669B2 JPH0213669B2 JP7262882A JP7262882A JPH0213669B2 JP H0213669 B2 JPH0213669 B2 JP H0213669B2 JP 7262882 A JP7262882 A JP 7262882A JP 7262882 A JP7262882 A JP 7262882A JP H0213669 B2 JPH0213669 B2 JP H0213669B2
- Authority
- JP
- Japan
- Prior art keywords
- methanol
- acetonitrile
- solvent
- water
- methoxycarbonylindole
- Prior art date
- 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
Links
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 239000002904 solvent Substances 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000013078 crystal Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- 238000001953 recrystallisation Methods 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 239000010446 mirabilite Substances 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 13
- -1 4-substituted indole Chemical class 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- 238000001035 drying Methods 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 238000000921 elemental analysis Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 238000000605 extraction Methods 0.000 description 5
- POJGICIDBWHZSQ-UHFFFAOYSA-N methyl 4-amino-3-(cyanomethyl)indole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)C=C(CC#N)C2=C1N POJGICIDBWHZSQ-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- WNCFBCKZRJDRKZ-UHFFFAOYSA-N 4-chloroindole-3-acetic acid Chemical compound C1=CC(Cl)=C2C(CC(=O)O)=CNC2=C1 WNCFBCKZRJDRKZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 4
- ZLBIYQIVGWLJHO-UHFFFAOYSA-N methyl 3-(cyanomethyl)-4-nitroindole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)C=C(CC#N)C2=C1[N+]([O-])=O ZLBIYQIVGWLJHO-UHFFFAOYSA-N 0.000 description 4
- WJLZJGWWMSKGKY-UHFFFAOYSA-N 1-(4-bromo-1h-indol-3-yl)-n,n-dimethylmethanamine Chemical compound C1=CC(Br)=C2C(CN(C)C)=CNC2=C1 WJLZJGWWMSKGKY-UHFFFAOYSA-N 0.000 description 3
- ILCMRTYGNSGRBS-UHFFFAOYSA-N 2-(4-nitro-1h-indol-3-yl)acetonitrile Chemical compound [O-][N+](=O)C1=CC=CC2=C1C(CC#N)=CN2 ILCMRTYGNSGRBS-UHFFFAOYSA-N 0.000 description 3
- LAVZKLJDKGRZJG-UHFFFAOYSA-N 4-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=CC2=C1C=CN2 LAVZKLJDKGRZJG-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- DFWPIGZKQYPHQZ-UHFFFAOYSA-N methyl 3-(cyanomethyl)-4-fluoroindole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)C=C(CC#N)C2=C1F DFWPIGZKQYPHQZ-UHFFFAOYSA-N 0.000 description 3
- YEJGFTSQENYASR-UHFFFAOYSA-N methyl 4-chloro-3-(cyanomethyl)indole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)C=C(CC#N)C2=C1Cl YEJGFTSQENYASR-UHFFFAOYSA-N 0.000 description 3
- NTWUAOHAQNZERF-UHFFFAOYSA-N n,n-dimethyl-1-(4-nitro-1h-indol-3-yl)methanamine Chemical compound C1=CC([N+]([O-])=O)=C2C(CN(C)C)=CNC2=C1 NTWUAOHAQNZERF-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- CGFUOBNYUICDPH-UHFFFAOYSA-N 2-(4-bromo-1h-indol-3-yl)acetonitrile Chemical compound BrC1=CC=CC2=C1C(CC#N)=CN2 CGFUOBNYUICDPH-UHFFFAOYSA-N 0.000 description 2
- QBQZALKPPLUCQY-UHFFFAOYSA-N 2-(4-fluoro-1h-indol-3-yl)acetic acid Chemical compound C1=CC(F)=C2C(CC(=O)O)=CNC2=C1 QBQZALKPPLUCQY-UHFFFAOYSA-N 0.000 description 2
- ZQFPMQFVJBELCS-UHFFFAOYSA-N 2-(4-iodo-1h-indol-3-yl)acetic acid Chemical compound C1=CC(I)=C2C(CC(=O)O)=CNC2=C1 ZQFPMQFVJBELCS-UHFFFAOYSA-N 0.000 description 2
- FPBHXYPVNWHLHT-UHFFFAOYSA-N 2-(4-iodo-1h-indol-3-yl)acetonitrile Chemical compound IC1=CC=CC2=C1C(CC#N)=CN2 FPBHXYPVNWHLHT-UHFFFAOYSA-N 0.000 description 2
- GRJZJFUBQYULKL-UHFFFAOYSA-N 4-bromo-1h-indole Chemical compound BrC1=CC=CC2=C1C=CN2 GRJZJFUBQYULKL-UHFFFAOYSA-N 0.000 description 2
- 239000003563 4-chloroindole-3-acetic acid Substances 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 238000000297 Sandmeyer reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 150000001989 diazonium salts Chemical class 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000006063 methoxycarbonylation reaction Methods 0.000 description 2
- RCEOZHBLULRIST-UHFFFAOYSA-N methyl 3-(cyanomethyl)-4-iodoindole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)C=C(CC#N)C2=C1I RCEOZHBLULRIST-UHFFFAOYSA-N 0.000 description 2
- 239000005648 plant growth regulator Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- GPYAFVBWLYCAMD-UHFFFAOYSA-N 1-(4-fluoro-1h-indol-3-yl)-n,n-dimethylmethanamine Chemical compound C1=CC(F)=C2C(CN(C)C)=CNC2=C1 GPYAFVBWLYCAMD-UHFFFAOYSA-N 0.000 description 1
- AQIDQZFQDRENOY-UHFFFAOYSA-N 2-(4-bromo-1h-indol-3-yl)acetic acid Chemical compound C1=CC(Br)=C2C(CC(=O)O)=CNC2=C1 AQIDQZFQDRENOY-UHFFFAOYSA-N 0.000 description 1
- IPYQJGRIWFMMMH-UHFFFAOYSA-N 2-(4-fluoro-1h-indol-3-yl)acetonitrile Chemical compound FC1=CC=CC2=C1C(CC#N)=CN2 IPYQJGRIWFMMMH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 229910020808 NaBF Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 238000007333 cyanation reaction Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical class C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- RUGAULALUBLSEG-UHFFFAOYSA-N methyl 4-aminoindole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)C=CC2=C1N RUGAULALUBLSEG-UHFFFAOYSA-N 0.000 description 1
- QLNAOKSQDONCTG-UHFFFAOYSA-N methyl 4-bromo-3-(cyanomethyl)indole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)C=C(CC#N)C2=C1Br QLNAOKSQDONCTG-UHFFFAOYSA-N 0.000 description 1
- FHOPBCYBMWVMGJ-UHFFFAOYSA-N methyl indole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)C=CC2=C1 FHOPBCYBMWVMGJ-UHFFFAOYSA-N 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Landscapes
- Indole Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7262882A JPS58189162A (ja) | 1982-04-30 | 1982-04-30 | ４位置換インド−ル誘導体の製造法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7262882A JPS58189162A (ja) | 1982-04-30 | 1982-04-30 | ４位置換インド−ル誘導体の製造法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58189162A JPS58189162A (ja) | 1983-11-04 |
| JPH0213669B2 true JPH0213669B2 (US06534493-20030318-C00166.png) | 1990-04-04 |
Family
ID=13494837
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7262882A Granted JPS58189162A (ja) | 1982-04-30 | 1982-04-30 | ４位置換インド−ル誘導体の製造法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58189162A (US06534493-20030318-C00166.png) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0448359U (US06534493-20030318-C00166.png) * | 1990-08-31 | 1992-04-24 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0866850A4 (en) * | 1995-11-30 | 2000-11-22 | Life Technologies Inc | AUXIN ANALOG |
-
1982
- 1982-04-30 JP JP7262882A patent/JPS58189162A/ja active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0448359U (US06534493-20030318-C00166.png) * | 1990-08-31 | 1992-04-24 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58189162A (ja) | 1983-11-04 |
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