Unlock instant, AI-driven research and patent intelligence for your innovation.

Crystal forms of n-[2-(diethylamino)ethyl]-5-[(5-fluoro-1,2-dihydro-2-oxo-3h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide and methods for their preparation

A technology for polymorphism and preparation of drugs, which is applied in N-[2-(diethylamino)ethyl]-5-[(5-fluoro-1,2-dihydro-2-oxo-3H- The crystal form of indole-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide and its preparation field can solve the problems that yellow-green solid cannot be obtained

Inactive Publication Date: 2011-02-02
RATIOPHARM GMBH
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, when these methods were repeated, a yellow-green solid could not be obtained

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Crystal forms of n-[2-(diethylamino)ethyl]-5-[(5-fluoro-1,2-dihydro-2-oxo-3h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide and methods for their preparation
  • Crystal forms of n-[2-(diethylamino)ethyl]-5-[(5-fluoro-1,2-dihydro-2-oxo-3h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide and methods for their preparation
  • Crystal forms of n-[2-(diethylamino)ethyl]-5-[(5-fluoro-1,2-dihydro-2-oxo-3h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide and methods for their preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0138] Example 1: Preparation of polymorph II of sunitinib

[0139] Sunitinib was obtained according to Example 35 (alternative synthesis) of EP 1255752B1. 0.25g of sunitinib was mixed with 50ml of acetone and heated to reflux. Then, 5 ml of toluene was added. The solvent was removed at 45°C under reduced pressure of 250 to 300 mmHg until precipitation of a crystalline solid occurred. The product was collected by filtration, washed with 2 ml of cold toluene, and dried at room temperature for 24 hours.

Embodiment 2

[0140] Example 2: Preparation of polymorph III of sunitinib

[0141] Sunitinib was obtained according to Example 35 (alternative synthesis) of EP 1255752B1. A suspension of sunitinib was prepared in a mixture of acetone and toluene (1:1 v / v) at room temperature (RT). The suspension was heated to reflux for 1 hour, resulting in complete dissolution of sunitinib. The solution was cooled to below the boiling temperature, and then further cooled with a mixture of ice and sodium chloride as external cooling for 24 hours. Without changing the ice bath, the mixture was allowed to warm to room temperature. Further crystallization at room temperature for 48 hours gave a yellow precipitate, which was removed by filtration. The dark orange filtrate was kept at room temperature until dark orange needles formed. These needles were separated and dried at room temperature for 24 hours.

Embodiment 3

[0142] Example 3: Preparation of polymorph III of sunitinib

[0143] Sunitinib crystal form II was refluxed in acetone to obtain a saturated solution. Filter off insoluble solids while hot, and seed the clear solution with Form III. The solvent was partially evaporated under vacuum using a water bath at 30-40°C, and the remaining solution was cooled to room temperature. The precipitate was filtered, washed with acetone, and dried in vacuo to obtain sunitinib free base in crystal form III.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
melting pointaaaaaaaaaa
Login to View More

Abstract

The present invention relates to novel crystal forms of Sunitinib and methods for their preparation.

Description

Technical field [0001] The present invention relates to Sunitinib (chemical name is N-[2-(diethylamino)ethyl]-5-[(5-fluoro-1,2-dihydro-2-oxo-3H -Indole-3-ylidene) methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide) new crystal form, and its preparation method. Background of the invention [0002] Sunitinib, under the trade name Marketed by Pfizer Pharma, it is a receptor tyrosine kinase inhibitor used to treat diseases such as renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Its activity depends on inhibiting cell signal transmission by targeting a variety of receptor tyrosine kinases, including platelet-derived growth factor receptors and vascular endothelial growth factor receptors. Since these two receptors are involved in tumor angiogenesis and tumor cell proliferation, inhibiting these targets at the same time leads to a decrease in tumor angiogenesis and cancer cell death. These effects led to the shrinkage of renal cell carcinoma and gastrointestinal str...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61P35/00C07D403/06A61K31/404
CPCC07D403/06A61P35/00
Inventor 内斯琳·莫哈迈德罗兰·波伊斯鲁迪格·拉茨汉斯-冈特·斯特里格尔
Owner RATIOPHARM GMBH