DE69912282T2 - Verfahren zur herstellung eines indolderivates - Google Patents
Verfahren zur herstellung eines indolderivates Download PDFInfo
- Publication number
- DE69912282T2 DE69912282T2 DE69912282T DE69912282T DE69912282T2 DE 69912282 T2 DE69912282 T2 DE 69912282T2 DE 69912282 T DE69912282 T DE 69912282T DE 69912282 T DE69912282 T DE 69912282T DE 69912282 T2 DE69912282 T2 DE 69912282T2
- Authority
- DE
- Germany
- Prior art keywords
- indole
- methyl
- carboxylate
- acid
- oxazino
- 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 - Lifetime
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000002253 acid Substances 0.000 claims abstract description 11
- LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- KVCSJPATKXABRQ-UHFFFAOYSA-N piboserod Chemical compound C1CN(CCCC)CCC1CNC(=O)C(C1=CC=CC=C11)=C2N1CCCO2 KVCSJPATKXABRQ-UHFFFAOYSA-N 0.000 claims description 11
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 7
- JOPOHNNCBFYVIM-UHFFFAOYSA-N methyl 3,4-dihydro-2h-[1,3]oxazino[3,2-a]indole-10-carboxylate Chemical compound C12=CC=CC=C2C(C(=O)OC)=C2N1CCCO2 JOPOHNNCBFYVIM-UHFFFAOYSA-N 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- SXSSVNBOMMHRRB-UHFFFAOYSA-N (1-butylpiperidin-4-yl)methanamine Chemical compound CCCCN1CCC(CN)CC1 SXSSVNBOMMHRRB-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 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 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 claims 2
- 229960005215 dichloroacetic acid Drugs 0.000 claims 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 abstract description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 abstract description 2
- IJQYPUZBTYDSGN-UHFFFAOYSA-N methyl 2-(3-chloropropoxy)-1h-indole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)=C(OCCCCl)NC2=C1 IJQYPUZBTYDSGN-UHFFFAOYSA-N 0.000 abstract 1
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
- RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QXAUTQFAWKKNLM-UHFFFAOYSA-N methyl indole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)=CNC2=C1 QXAUTQFAWKKNLM-UHFFFAOYSA-N 0.000 description 2
- FXCLGAGFIKPOQS-UHFFFAOYSA-N n-[(1-butylpiperidin-4-yl)methyl]-1h-indole-3-carboxamide Chemical compound C1CN(CCCC)CCC1CNC(=O)C1=CNC2=CC=CC=C12 FXCLGAGFIKPOQS-UHFFFAOYSA-N 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- BHNHHSOHWZKFOX-UHFFFAOYSA-N 2-methyl-1H-indole Chemical compound C1=CC=C2NC(C)=CC2=C1 BHNHHSOHWZKFOX-UHFFFAOYSA-N 0.000 description 1
- 0 CCCCN1CCC([*-]C2=C3OCCCN3C3C=CC=CC23)CC1 Chemical compound CCCCN1CCC([*-]C2=C3OCCCN3C3C=CC=CC23)CC1 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- HAPIXNBOBZHNCA-UHFFFAOYSA-N methyl 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate Chemical compound COC(=O)C1=CC=C(C)C(B2OC(C)(C)C(C)(C)O2)=C1 HAPIXNBOBZHNCA-UHFFFAOYSA-N 0.000 description 1
- -1 oxazinoindole compound Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000003523 serotonin 4 antagonist Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9815481.8A GB9815481D0 (en) | 1998-07-16 | 1998-07-16 | Pharmaceuticals |
| GB9815481 | 1998-07-16 | ||
| PCT/EP1999/004944 WO2000003984A1 (en) | 1998-07-16 | 1999-07-13 | Process for the preparation of an indole derivate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69912282D1 DE69912282D1 (de) | 2003-11-27 |
| DE69912282T2 true DE69912282T2 (de) | 2004-07-29 |
Family
ID=10835640
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69912282T Expired - Lifetime DE69912282T2 (de) | 1998-07-16 | 1999-07-13 | Verfahren zur herstellung eines indolderivates |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1097136B1 (https=) |
| JP (1) | JP3842556B2 (https=) |
| AT (1) | ATE252557T1 (https=) |
| CA (1) | CA2337382C (https=) |
| DE (1) | DE69912282T2 (https=) |
| ES (1) | ES2209476T3 (https=) |
| GB (1) | GB9815481D0 (https=) |
| WO (1) | WO2000003984A1 (https=) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0211230D0 (en) | 2002-05-16 | 2002-06-26 | Medinnova Sf | Treatment of heart failure |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3911297B2 (ja) * | 1996-08-16 | 2007-05-09 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | Ｎ―［（１―ｎブチル―４―ピペリジル）メチル］―３，４―ジヒドロ―２Ｈ―［１，３］オキサジノ［３，２―ａ］インドール―１０―カルボキシアミドおよび塩ならびに製造における中間体 |
-
1998
- 1998-07-16 GB GBGB9815481.8A patent/GB9815481D0/en not_active Ceased
-
1999
- 1999-07-13 JP JP2000560093A patent/JP3842556B2/ja not_active Expired - Fee Related
- 1999-07-13 WO PCT/EP1999/004944 patent/WO2000003984A1/en not_active Ceased
- 1999-07-13 CA CA002337382A patent/CA2337382C/en not_active Expired - Fee Related
- 1999-07-13 DE DE69912282T patent/DE69912282T2/de not_active Expired - Lifetime
- 1999-07-13 AT AT99938234T patent/ATE252557T1/de not_active IP Right Cessation
- 1999-07-13 ES ES99938234T patent/ES2209476T3/es not_active Expired - Lifetime
- 1999-07-13 EP EP99938234A patent/EP1097136B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ES2209476T3 (es) | 2004-06-16 |
| EP1097136A1 (en) | 2001-05-09 |
| WO2000003984A1 (en) | 2000-01-27 |
| GB9815481D0 (en) | 1998-09-16 |
| JP2002520392A (ja) | 2002-07-09 |
| EP1097136B1 (en) | 2003-10-22 |
| CA2337382A1 (en) | 2000-01-27 |
| DE69912282D1 (de) | 2003-11-27 |
| CA2337382C (en) | 2008-04-08 |
| ATE252557T1 (de) | 2003-11-15 |
| JP3842556B2 (ja) | 2006-11-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |