CN102977083A - New crystal form XVII of 1-(4-(5-cyanoindole-3-yl) butyl)-4-(2-carbamyl-benzofuran-5-yl)-piperazine hydrochloride and preparation method of new crystal form XVII - Google Patents
New crystal form XVII of 1-(4-(5-cyanoindole-3-yl) butyl)-4-(2-carbamyl-benzofuran-5-yl)-piperazine hydrochloride and preparation method of new crystal form XVII Download PDFInfo
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- CN102977083A CN102977083A CN2012105443223A CN201210544322A CN102977083A CN 102977083 A CN102977083 A CN 102977083A CN 2012105443223 A CN2012105443223 A CN 2012105443223A CN 201210544322 A CN201210544322 A CN 201210544322A CN 102977083 A CN102977083 A CN 102977083A
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Abstract
The invention relates to a new crystal form XVII of 1-(4-(5-cyanoindole-3-yl) butyl)-4-(2-carbamyl-benzofuran-5-yl)-piperazine hydrochloride and a preparation method of the new crystal form XVII. Peaks of an X-ray diffraction pattern of powder of the new crystal form XVII are located at 9.02 degrees, 9.96 degrees, 13.06 degrees, 20.90 degrees, 21.32 degrees, 22.94 degrees, 23.70 degrees and 24.62 degrees+/-0.2 degrees and 2 theta, initial melting is shown at about 277 DEG C in a differential scanning calorimetry spectrum, and thermogravimetric analysis shows that the product has no water of crystallization.
Description
Invention field
The present invention relates to organic chemistry filed and pharmaceutical field, be specifically related to formula (I) 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-the yl)-new crystal form X VII of piperazine hydrochloride and method of preparation thereof.
Background technology
Some crystallinity of medical compounds, be that the morphology form may help to develop suitable formulation, because if the morphology form does not keep constant in clinical and stability study, the definite dosage that uses or measure may not have comparability between two batches.In case prepared the compound that practicality is arranged, importantly be familiar with the morphology form that in every kind of formulation, presents, use the same form to guarantee the preparation method, in every part of metering, comprise the medicine of equivalent.
1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride has now found that 16 kinds of different pure crystal and their preparation method, wherein 6 kinds of solvate crystal formations can not be used for medicine, 3 kinds of hydrate crystal forms less stable, 4 kinds of dehydrate crystal formation solvability differences are larger, the rest is 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine dihydrochloride is not used in medicine, and above crystal formation is all different from the present invention.The invention provides 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII and preparation method.
From Chinese patent CN 100384841C, US Patent No. 5532241 and WO 00/72832 known 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine, its physiology on acceptable salt, can prepare it/their method and their purposes some medical conditions for the treatment of, wherein China is authorized form IV.Form IV and the present invention all are applicable to common oral preparation.
Summary of the invention
One of purpose of the present invention provides a kind of 1-[4-(5-cyanoindole-3-yl) butyl]-the new crystal form X VII of 4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride.
More specifically, the present invention relates to 1-[4-(5-cyanoindole-3-yl) butyl of formula (I) compound]-the new crystal form X VII of 4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride, it characterizes by following powder x-ray diffraction figure, use the anticathode diffractometer of copper to measure, represent that with spacing d, 2 θ angles, Prague and relative intensity I/I0 described relative intensity represents with the strongest ray percentage ratio:
| Sequence number | 2θ | d | I/I0 |
| 1 | 9.02 | 9.796 | 21 |
| 2 | 9.96 | 8.873 | 16 |
| 3 | 13.06 | 6.773 | 41 |
| 4 | 20.90 | 4.247 | 74 |
| 5 | 21.32 | 4.164 | 99 |
| 6 | 22.94 | 3.874 | 44 |
| 7 | 23.70 | 3.751 | 57 |
| 8 | 24.62 | 3.613 | 50 |
The 1-[4-of formula (I) compound (5-cyanoindole-3-yl) butyl]-the new crystal form X VII of 4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride, determine with dsc method is presented at 277 ℃ of left and right sides incipient meltings, and thermogravimetric analysis shows that this product is without crystal water.By the heat analysis, in 30 to 350 ℃ scope, measure, can further characterize X VII type.Accompanying drawing 2, accompanying drawing 3 show respectively the measuring result of TGA and DSC.The present invention 50 to 100 ℃ for sloughing the free-water process, fusing about 277 ℃.
The invention still further relates to 1-[4-(5-cyanoindole-3-yl) butyl]-preparation method of the new crystal form X VII of 4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride, the method comprises following steps:
(1) with 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine is dispersed in the tetrahydrofuran (THF); Under the temperature between 20 and 30 ℃, add aqueous hydrochloric acid, at room temperature separate out precipitation, by the filtered and recycled precipitation, get 1-[4-(5-cyanoindole-3-yl) butyl 85 to 90 ℃ of vacuum-dryings]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride;
(2) with 1-[4-(5-cyanoindole-3-yl) butyl that obtains]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride mixes according to 1: 5 to 1: 10 ratio with water, stirs; Separate out precipitation under the room temperature, precipitate by filtered and recycled, 50 to 120 ℃ of vacuum-dryings or 80 to 150 ℃, preferred 80 to 90 ℃ of vacuum-dryings or 100 to 130 ℃ of dryings, dry 1-[4-(5-cyanoindole-3-yl) butyl that gets]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII.
1-[4-(5-cyanoindole-3-yl) butyl for preparing by the method]-the new crystal form X VII of 4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride, purity is good, have very definite crystal formation and circulation ratio fabulous.The characteristics such as that this kind method also has is economical and practical, good stability, easy and simple to handle, environmental protection.
Description of drawings
Accompanying drawing 1 is 1-[4-(5-cyanoindole-3-yl) butyl]-the powder x-ray diffraction figure of 4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII, 2 θ angles are ordinate zou as X-coordinate, intensity take Prague;
Accompanying drawing 2 is 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII thermogravimetric analysis figure;
Accompanying drawing 3 is 1-[4-(5-cyanoindole-3-yl) butyl]-the dsc figure of 4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII.
Embodiment
Embodiment 1,1-[4-(5-cyanoindole-3-yl) butyl]-preparation of 4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII
To 10g 1-[4-(5-cyanoindole-3-yl) butyl]-326g tetrahydrofuran solution that 4-(2-carboxamide-cumarone-5-yl)-piperazine disperses adds 21g hydrochloric acid (37%).After the stirring, the crystal that precipitates is carried out suction filtration, in 85 to 90 ℃ of vacuum, is dried to constant weight, obtain 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride.With 1-[4-(5-cyanoindole-3-yl) butyl that obtains]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride mixes according to 1: 5 to 1: 10 ratio with water, after the stirring, the crystal that precipitates is carried out suction filtration, 80 to 90 ℃ of vacuum-dryings to constant weight, dry 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII.
Claims (4)
1. compound formula (I) 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII,
It characterizes by following powder x-ray diffraction figure, uses the anticathode diffractometer of copper to measure, and represents that with spacing d, 2 θ angles, Prague and relative intensity I/I0 described relative intensity represents with the strongest ray percentage ratio:
2. compound formula as claimed in claim 1 (I) 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII, determine with dsc method is presented at 277 ℃ of left and right sides incipient meltings.
3. compound formula as claimed in claim 1 (I) 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII, thermogravimetric analysis shows that this product is without crystal water.
4. compound formula (I) 1-[4-(5-cyanoindole-3-yl) butyl described in claim 1 or 2 or 3]-preparation method of 4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII comprises:
(1) with 1-[4-(5-cyanoindole-3-yl) butyl]-4-(2-carboxamide-cumarone-5-yl)-piperazine is dispersed in the tetrahydrofuran (THF); Under the temperature between 20 and 30 ℃, add aqueous hydrochloric acid, at room temperature separate out precipitation, by the filtered and recycled precipitation, get 1-[4-(5-cyanoindole-3-yl) butyl 85 to 90 ℃ of vacuum-dryings]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride;
(2) with 1-[4-(5-cyanoindole-3-yl) butyl that obtains]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride mixes according to 1: 5 to 1: 10 ratio with water, stirs; Separate out precipitation under the room temperature, precipitate by filtered and recycled, 50 to 120 ℃ of vacuum-dryings or 80 to 150 ℃, preferred 80 to 90 ℃ of vacuum-dryings or 100 to 130 ℃ of dryings, dry 1-[4-(5-cyanoindole-3-yl) butyl that gets]-4-(2-carboxamide-cumarone-5-yl)-piperazine hydrochloride new crystal form X VII.
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| CN2012105443223A CN102977083A (en) | 2012-12-17 | 2012-12-17 | New crystal form XVII of 1-(4-(5-cyanoindole-3-yl) butyl)-4-(2-carbamyl-benzofuran-5-yl)-piperazine hydrochloride and preparation method of new crystal form XVII |
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| CN2012105443223A CN102977083A (en) | 2012-12-17 | 2012-12-17 | New crystal form XVII of 1-(4-(5-cyanoindole-3-yl) butyl)-4-(2-carbamyl-benzofuran-5-yl)-piperazine hydrochloride and preparation method of new crystal form XVII |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014049612A3 (en) * | 2012-09-27 | 2014-05-22 | Msn Laboratories Limited | Processes and polymorphs of 5-[4-[4-(5-cyano-1h-indol-3-yl) butyl]-1-piperazinyl]-2-benzofuran carboxamide and its salts |
| WO2015102019A3 (en) * | 2013-12-30 | 2015-08-27 | Msn Laboratories Private Limited | Process for the preparation of polymorphs of 5-[4-[4-(5-cyano-1h-indol-3-yl)butyl]-1-piperazinyl]-2-benzofuran carboxamide hydrochloride |
| US9382233B2 (en) | 2012-06-13 | 2016-07-05 | Apotex Inc. | Forms of vilazodone and processes for the preparation thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1106811A (en) * | 1993-09-30 | 1995-08-16 | 默克专利股份有限公司 | Piperidines and piperazines |
| WO2000072832A2 (en) * | 1999-05-27 | 2000-12-07 | Merck Patent Gmbh | Novel use of 1-[4-(cyanoindol-3yl)butyl]-4-(carbamoyl-benzofuran-5yl)-piperazine and its physiologically acceptable salts |
| CN1516699A (en) * | 2001-06-19 | 2004-07-28 | Ĭ��ר���ɷ�����˾ | Polymorphic forms of 1-4-(5-cyanoindol-3-yl) butyl-4-(2-carbamoylbenzofuran-5-yl) piperazine hydrochloride |
| CN102267985A (en) * | 2011-06-15 | 2011-12-07 | 上海医药工业研究院 | Preparation method for vilazodone and hydrochloride thereof |
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- 2012-12-17 CN CN2012105443223A patent/CN102977083A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1106811A (en) * | 1993-09-30 | 1995-08-16 | 默克专利股份有限公司 | Piperidines and piperazines |
| WO2000072832A2 (en) * | 1999-05-27 | 2000-12-07 | Merck Patent Gmbh | Novel use of 1-[4-(cyanoindol-3yl)butyl]-4-(carbamoyl-benzofuran-5yl)-piperazine and its physiologically acceptable salts |
| CN1516699A (en) * | 2001-06-19 | 2004-07-28 | Ĭ��ר���ɷ�����˾ | Polymorphic forms of 1-4-(5-cyanoindol-3-yl) butyl-4-(2-carbamoylbenzofuran-5-yl) piperazine hydrochloride |
| CN102267985A (en) * | 2011-06-15 | 2011-12-07 | 上海医药工业研究院 | Preparation method for vilazodone and hydrochloride thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9382233B2 (en) | 2012-06-13 | 2016-07-05 | Apotex Inc. | Forms of vilazodone and processes for the preparation thereof |
| WO2014049612A3 (en) * | 2012-09-27 | 2014-05-22 | Msn Laboratories Limited | Processes and polymorphs of 5-[4-[4-(5-cyano-1h-indol-3-yl) butyl]-1-piperazinyl]-2-benzofuran carboxamide and its salts |
| WO2015102019A3 (en) * | 2013-12-30 | 2015-08-27 | Msn Laboratories Private Limited | Process for the preparation of polymorphs of 5-[4-[4-(5-cyano-1h-indol-3-yl)butyl]-1-piperazinyl]-2-benzofuran carboxamide hydrochloride |
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Application publication date: 20130320 |