A process for purification of carfilzomib

一种卡非佐米、草酸卡的技术，应用在还原通常在合成卡非佐米期间形成的乙酰胺杂质领域，达到容易成本的效果

Inactive Publication Date: 2018-01-05
FRESENIUS KABI ONCOLOGY LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] Inevitably formed in the prior art processes described in U.S. Patent Nos. 7,417,042, 7,232,818, and 8,207,297, and this impurity is difficult to separate from the desired end product

Method used

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  • A process for purification of carfilzomib
  • A process for purification of carfilzomib
  • A process for purification of carfilzomib

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0063] a) preparation of carfilzomib oxalate:

[0064] Crude carfilzomib (10 g) and oxalic acid (1.31 g) were dissolved in a mixture of tetrahydrofuran (70 ml) and acetonitrile (50 ml), and stirred at 20-25°C for 1 hour.

[0065] After 1 hour the reaction mixture was cooled to 0-10°C and stirred for 3 hours, then the formed precipitate was filtered to give carfilzomib oxalate.

[0066] Carfilzomib oxalate: X-ray powder diffraction pattern (XRPD) with characteristic peaks at the following (2θ±0.2 degrees): 4.06, 4.66, 6.99, 8.07, 8.46, 9.30, 10.72 and 14.84

[0067] b) Preparation of Carfilzomib:

[0068] Precipitated carfilzomib oxalate as a wet cake obtained in Example-1 was dissolved in dichloromethane (100 ml), followed by washing with sodium bicarbonate solution (100 ml) and water (100 ml). The organic layer was concentrated under reduced pressure and the product was crystallized in ethyl acetate / methyl tert-butyl ether mixture (200ml) (3:7) to give carfilzomib (8g).

...

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Abstract

The present invention relates to a process for the purification of Carfiizomib of Formula II that reduces the level of an acetaniide impurity of Formula II preferably below 0.10 wt%. Formula I FormulaII.

Description

technical field [0001] The present invention relates to a method for the purification of carfilzomib, in particular the reduction of the acetamide impurity normally formed during the synthesis of carfilzomib. Background technique [0002] Carfilzomib, (2S)-N-{(1S)-1-benzyl-2-[((1S)-3-methyl-1-{[(2R)-2-methyloxirane -2-yl]carbonyl}butyl)amino]-2-oxoethyl}-4-methyl-2-({(2S)-2-[(morpholin-4-ylacetyl)amino]- 4-phenylbutyryl}amino)pentanamide is represented by formula I: [0003] [0004] Carfilzomib (CFZ, sold under the tradename Kyprolis, Onyx Pharmaceuticals, Inc.) is a tetrapeptide epoxyketone and selective protease inhibitor. It is an analog of epoxomicin. [0005] It was approved by the U.S. Food and Drug Administration (FDA) on July 20, 2012 for use in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma who have received 1-3 prior lines treated patients. It is also indicated for patients with multiple myeloma who have received...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K1/30
CPCC07K5/1008A61P35/00C07K1/02C07K5/101
Inventor M·K·潘迪R·N·蒂瓦里S·S·索希G·辛格S·拉希里W·卡布里
Owner FRESENIUS KABI ONCOLOGY LTD
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