CA2337248C - Process for the preparation of an indole derivative - Google Patents
Process for the preparation of an indole derivative Download PDFInfo
- Publication number
- CA2337248C CA2337248C CA2337248A CA2337248A CA2337248C CA 2337248 C CA2337248 C CA 2337248C CA 2337248 A CA2337248 A CA 2337248A CA 2337248 A CA2337248 A CA 2337248A CA 2337248 C CA2337248 C CA 2337248C
- Authority
- CA
- Canada
- Prior art keywords
- formula
- compound
- reaction
- methyl
- dimethylpiperazine
- 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 - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 150000002475 indoles Chemical class 0.000 title description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims abstract description 24
- 150000003512 tertiary amines Chemical class 0.000 claims abstract description 15
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000012973 diazabicyclooctane Substances 0.000 claims abstract description 9
- 230000000269 nucleophilic effect Effects 0.000 claims abstract description 6
- SBXYTQUGWXISRE-UHFFFAOYSA-N methyl 3-chloroindole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)(Cl)C=NC2=C1 SBXYTQUGWXISRE-UHFFFAOYSA-N 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 45
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical group CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 claims description 36
- 150000001875 compounds Chemical class 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 claims description 14
- QXAUTQFAWKKNLM-UHFFFAOYSA-N methyl indole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)=CNC2=C1 QXAUTQFAWKKNLM-UHFFFAOYSA-N 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- -1 butyl-4-piperidyl Chemical group 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- 239000002002 slurry Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 3
- 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 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 3
- 235000011152 sodium sulphate Nutrition 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims 3
- SXSSVNBOMMHRRB-UHFFFAOYSA-N (1-butylpiperidin-4-yl)methanamine Chemical compound CCCCN1CCC(CN)CC1 SXSSVNBOMMHRRB-UHFFFAOYSA-N 0.000 claims 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 4
- 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
- KVCSJPATKXABRQ-UHFFFAOYSA-N piboserod Chemical compound C1CN(CCCC)CCC1CNC(=O)C(C1=CC=CC=C11)=C2N1CCCO2 KVCSJPATKXABRQ-UHFFFAOYSA-N 0.000 description 7
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- LSGKMZLPZFPAIN-UHFFFAOYSA-N 1h-indole-3-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CNC2=C1 LSGKMZLPZFPAIN-UHFFFAOYSA-N 0.000 description 4
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000010961 commercial manufacture process Methods 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
- 239000012971 dimethylpiperazine Substances 0.000 description 1
- 239000003814 drug Substances 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
- 239000004615 ingredient Substances 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000000926 separation method Methods 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)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9815483.4A GB9815483D0 (en) | 1998-07-16 | 1998-07-16 | Pharmaceuticals |
| GB9815483.4 | 1998-07-16 | ||
| PCT/EP1999/004943 WO2000003983A1 (en) | 1998-07-16 | 1999-07-13 | Process for the preparation of an indole derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2337248A1 CA2337248A1 (en) | 2000-01-27 |
| CA2337248C true CA2337248C (en) | 2011-04-19 |
Family
ID=10835641
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2337248A Expired - Fee Related CA2337248C (en) | 1998-07-16 | 1999-07-13 | Process for the preparation of an indole derivative |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1097135B1 (https=) |
| JP (2) | JP3842555B2 (https=) |
| AT (1) | ATE394374T1 (https=) |
| CA (1) | CA2337248C (https=) |
| DE (1) | DE69938661D1 (https=) |
| ES (1) | ES2307339T3 (https=) |
| GB (1) | GB9815483D0 (https=) |
| WO (1) | WO2000003983A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020091271A1 (en) | 1998-07-16 | 2002-07-11 | Smithkline Beecham Plc | Process for the preparation of an indole derivative |
| GB0211230D0 (en) | 2002-05-16 | 2002-06-26 | Medinnova Sf | Treatment of heart failure |
| WO2020061045A1 (en) | 2018-09-18 | 2020-03-26 | Leidos, Inc. | Sensor array multiplexer |
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 GBGB9815483.4A patent/GB9815483D0/en not_active Ceased
-
1999
- 1999-07-13 JP JP2000560092A patent/JP3842555B2/ja not_active Expired - Fee Related
- 1999-07-13 DE DE69938661T patent/DE69938661D1/de not_active Expired - Lifetime
- 1999-07-13 EP EP99938233A patent/EP1097135B1/en not_active Expired - Lifetime
- 1999-07-13 AT AT99938233T patent/ATE394374T1/de not_active IP Right Cessation
- 1999-07-13 ES ES99938233T patent/ES2307339T3/es not_active Expired - Lifetime
- 1999-07-13 WO PCT/EP1999/004943 patent/WO2000003983A1/en not_active Ceased
- 1999-07-13 CA CA2337248A patent/CA2337248C/en not_active Expired - Fee Related
-
2006
- 2006-03-20 JP JP2006076859A patent/JP4511484B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP3842555B2 (ja) | 2006-11-08 |
| CA2337248A1 (en) | 2000-01-27 |
| EP1097135A1 (en) | 2001-05-09 |
| ATE394374T1 (de) | 2008-05-15 |
| WO2000003983A1 (en) | 2000-01-27 |
| JP2006176539A (ja) | 2006-07-06 |
| EP1097135B1 (en) | 2008-05-07 |
| GB9815483D0 (en) | 1998-09-16 |
| DE69938661D1 (de) | 2008-06-19 |
| ES2307339T3 (es) | 2008-11-16 |
| JP2002520391A (ja) | 2002-07-09 |
| JP4511484B2 (ja) | 2010-07-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |