Method for preparing pyrazole derivative

A kind of technology of compound and organic solvent, applied in the field of preparation of pyrazole derivatives

Inactive Publication Date: 2015-03-25
SUNSHINE LAKE PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The invention provides a preparation method of compound (02), which solves the problem of high-temperature and long-time reaction in the prior art, and the product has high purity and high yield, and the method is easy to operate and low in cost, and is suitable for industrial production

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  • Method for preparing pyrazole derivative
  • Method for preparing pyrazole derivative
  • Method for preparing pyrazole derivative

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specific Embodiment approach

[0025] In order to enable those skilled in the art to better understand the technical solutions of the present invention, some non-limiting examples are further disclosed below to further describe the present invention in detail.

[0026] The reagents used in the present invention can be purchased from the market or can be prepared by the methods described in the present invention.

[0027] In the present invention, g means gram, and mL means milliliter.

Embodiment 1

[0029] Into the reactor, add 10.00 g of 3-amino-5-(4-phenoxyphenyl)-4-cyano-1H-pyrazole, 7.61 g of formamidine acetate and 100 mL of n-butanol, and stir evenly at room temperature. Heat up to 110°C and react at 110°C for 15 hours. Then the reaction mixture was cooled to 20°C-30°C, filtered, and the filter cake was rinsed with 20mL of n-butanol, and the obtained solid was vacuum-dried to dryness at 60°C to obtain 10.21g of solid, which was confirmed by mass spectrometry and nuclear magnetic spectrum. -(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine, purity: 99.43%.

[0030] Mass spectrum MS: 304.90;

[0031] NMR 1 H NMR (600MHz, DMSO) δ13.55(s, 1H), 8.22(s, 1H), 7.67(d, J=8.5Hz, 2H), 7.44(t, J=7.8Hz, 2H), 7.16(ddd , J=21.5, 13.8, 7.7Hz, 5H).

Embodiment 2

[0033] Into the reactor, add 10.00 g of 3-amino-5-(4-phenoxyphenyl)-4-cyano-1H-pyrazole, 6.74 g of formamidine acetate and 80 mL of n-butanol, and stir evenly at room temperature. Heat up to 100°C-110°C, and react at 100°C-110°C for 16 hours. Then the reaction mixture was cooled to 10°C-20°C, filtered, and the filter cake was rinsed with 20mL of n-butanol, and the obtained solid was vacuum-dried to dryness at 70°C to obtain 10.28g of solid, purity: 99.21%, confirmed by mass spectrometry as 3 -(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine.

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Abstract

The invention relates to a method for preparing a pyrazole derivative for preparing ibrutinib, and belongs to the technical field of pharmacy. The method comprises the following steps: reacting raw materials with formamidine acetate in an organic solvent at 80-130 DEG C, cooling after the reaction is completed, and collecting solids to obtain a product, wherein the organic solvent is one or more of N,N-dimethyl formamide, N,N-dimethylacetamide, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, glycol dimethyl ether, n-butyl alcohol, isobutanol, n-amyl alcohol and isoamyl alcohol. The method can be used for solving the problem of long-time high temperature reaction in the prior art, is simple and convenient, is low in cost, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of pyrazole derivatives, which belongs to the technical field of pharmacy. Background technique [0002] Ibrutinib, chemical name 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine -1-yl]-1-piperidinyl]-2-propen-1-one; is an irreversible Bruton's tyrosine kinase (BTK, Bruton's tyrosine kinase) inhibitor, which can inhibit the proliferation of malignant B cells , survival, and can be used to treat diseases such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). [0003] In the process of preparing ibrutinib, the intermediate compound 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine needs to be prepared first, and its structure is as follows: As shown in (02): [0004] [0005] In the prior art, compound (02) is usually prepared by reacting at a high temperature of 180°C for a long time; this method has a high reaction temperature and a long reaction time, resu...

Claims

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Application Information

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IPC IPC(8): C07D487/04
CPCC07D487/04
Inventor 李华姚博杨凤智肖毅
Owner SUNSHINE LAKE PHARM CO LTD
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