ES2307339T3 - Proceso para la preparacion de un derivado de indol. - Google Patents
Proceso para la preparacion de un derivado de indol. Download PDFInfo
- Publication number
- ES2307339T3 ES2307339T3 ES99938233T ES99938233T ES2307339T3 ES 2307339 T3 ES2307339 T3 ES 2307339T3 ES 99938233 T ES99938233 T ES 99938233T ES 99938233 T ES99938233 T ES 99938233T ES 2307339 T3 ES2307339 T3 ES 2307339T3
- Authority
- ES
- Spain
- Prior art keywords
- formula
- compound
- methyl
- indole
- procedure
- 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
- 238000000034 method Methods 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title abstract description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims abstract description 18
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012973 diazabicyclooctane Substances 0.000 claims abstract description 7
- 230000000269 nucleophilic effect Effects 0.000 claims abstract description 4
- 150000003512 tertiary amines Chemical class 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- 150000001875 compounds Chemical class 0.000 claims description 23
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical group CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 10
- KVCSJPATKXABRQ-UHFFFAOYSA-N piboserod Chemical compound C1CN(CCCC)CCC1CNC(=O)C(C1=CC=CC=C11)=C2N1CCCO2 KVCSJPATKXABRQ-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- QXAUTQFAWKKNLM-UHFFFAOYSA-N methyl indole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)=CNC2=C1 QXAUTQFAWKKNLM-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000000725 suspension 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
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 claims description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 238000007363 ring formation reaction Methods 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- WYNCBMVWNGMOJN-UHFFFAOYSA-N 3-chloroindole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)(Cl)C=NC2=C1 WYNCBMVWNGMOJN-UHFFFAOYSA-N 0.000 claims description 2
- 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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- TXSPITKKVMLDDL-UHFFFAOYSA-N pyrrolo[2,3-f][2,1]benzoxazine Chemical compound C1=CC2=NOC=CC2=C2C1=CC=N2 TXSPITKKVMLDDL-UHFFFAOYSA-N 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- UABVCZHWRUGYSR-UHFFFAOYSA-N n-[(1-butylpiperidin-4-yl)methyl]-3,4-dihydro-2h-[1,3]oxazino[3,2-a]indole-10-carboxamide;hydrochloride Chemical compound Cl.C1CN(CCCC)CCC1CNC(=O)C(C1=CC=CC=C11)=C2N1CCCO2 UABVCZHWRUGYSR-UHFFFAOYSA-N 0.000 claims 1
- 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
- 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 abstract 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002475 indoles Chemical class 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
- 230000002035 prolonged effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000012777 commercial manufacturing 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 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 description 1
- 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 description 1
- -1 oxazinoindole compound Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000000926 separation method Methods 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
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9815483 | 1998-07-16 | ||
| GBGB9815483.4A GB9815483D0 (en) | 1998-07-16 | 1998-07-16 | Pharmaceuticals |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2307339T3 true ES2307339T3 (es) | 2008-11-16 |
Family
ID=10835641
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99938233T Expired - Lifetime ES2307339T3 (es) | 1998-07-16 | 1999-07-13 | Proceso para la preparacion de un derivado de indol. |
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 |
| CA2337248C (en) | 2011-04-19 |
| JP2006176539A (ja) | 2006-07-06 |
| EP1097135B1 (en) | 2008-05-07 |
| GB9815483D0 (en) | 1998-09-16 |
| DE69938661D1 (de) | 2008-06-19 |
| JP2002520391A (ja) | 2002-07-09 |
| JP4511484B2 (ja) | 2010-07-28 |
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