Check patentability & draft patents in minutes with Patsnap Eureka AI!

Preparation method of 2-methyl-4-amino-6-chloropyrimidine

A technology of methylpyrimidine and chloropyrimidine, which is applied in the field of preparation of 2-methyl-4-amino-6-chloropyrimidine, can solve problems such as poor economic benefits and environmental impact, difficult reactions, complicated operations, etc., and achieve simplification Reaction process and post-treatment process, reduce production cost, optimize the effect of preparation process

Active Publication Date: 2017-03-08
SHANGHAI ZAIQI BIO TECH
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] As described in the follow-up comparative examples 1 and 2, in the prior art, the yield of the synthesis process of 2-methyl-4-amino-6-chloropyrimidine is only 68%, the operation is complicated, the reaction is difficult, the yield is low, and it is economical. Poor benefits and environmental impact

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
  • Preparation method of 2-methyl-4-amino-6-chloropyrimidine
  • Preparation method of 2-methyl-4-amino-6-chloropyrimidine
  • Preparation method of 2-methyl-4-amino-6-chloropyrimidine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] The first step: the synthesis of 4,6-dichloro-2-methylpyrimidine

[0021] 4,6-Dihydroxy-2-methylpyrimidine (5.0g, 0.04mol) was added to a mixed solution of phosphorus oxychloride (18.4g, 0.12mol) and acetonitrile, and the reaction was stirred at 60°C for 3 hours, and confirmed by spotting Raw material points disappear. The excess phosphorus oxychloride was distilled under reduced pressure, and the residue was poured into 50 g of ice water. The precipitated solid was filtered and purified by column to obtain 6 g (yield: 92%) of solid.

[0022] After nuclear magnetic detection, the nuclear magnetic spectrum is as follows, and the solid can be determined to be 4,6-dichloro-2-methylpyrimidine.

[0023] 1H NMR (CDCl3, 400MHz): d 2.63 (s, 3H, CH3), 7.17 [s, ​​1H, H (5)].

[0024] The second step: the synthesis of 2-methyl-4-amino-6-chloropyrimidine

[0025] Add 4,6-dichloro-2-methylpyrimidine (50g, 0.31mol) and ammonia water (0.5L) into a 1L reaction flask, stir at 40°C fo...

Embodiment 2

[0030] The first step: the synthesis of 4,6-dichloro-2-methylpyrimidine

[0031] 4,6-dihydroxy-2-methylpyrimidine (5.0g, 0.04mol) was added to a mixed solution of phosphorus oxychloride (12.26g, 0.08mol) and acetonitrile, and the reaction was stirred at 70°C for 3 hours, and confirmed by spotting Raw material points disappear. The excess phosphorus oxychloride was distilled under reduced pressure, and the residue was poured into 50 g of ice water. The precipitated solid was filtered and purified by column to obtain 5.8 g (yield: 90%) of solid.

[0032] Through nuclear magnetic detection, the solid can be determined to be 4,6-dichloro-2-methylpyrimidine.

[0033] The second step: the synthesis of 2-methyl-4-amino-6-chloropyrimidine

[0034] Add 4,6-dichloro-2-methylpyrimidine (50g, 0.31mol) and a mixed solution of ammonia water and tetrahydrofuran (0.5L) into a 1L reaction flask, stir at 45°C for 5 hours, cool the reaction to room temperature, filter, and use Wash with petro...

Embodiment 3

[0038] The first step: the synthesis of 4,6-dichloro-2-methylpyrimidine

[0039] 4,6-dihydroxy-2-methylpyrimidine (5.0g, 0.04mol) was added to a mixed solution of thionyl chloride (18.9g, 0.16mol) and acetonitrile, and the reaction was stirred at 80°C for 3 hours, and confirmed by spotting Raw material points disappear. The excess thionyl chloride was distilled under reduced pressure, and the residue was poured into 50 g of ice water. The precipitated solid was filtered and purified by column to obtain 6.1 g (yield: 94%) of solid.

[0040] Through nuclear magnetic detection, the solid can be determined to be 4,6-dichloro-2-methylpyrimidine.

[0041] The second step: the synthesis of 2-methyl-4-amino-6-chloropyrimidine

[0042] Add 4,6-dichloro-2-methylpyrimidine (50g, 0.31mol) and methanolic ammonia solution (0.5L) into a 1L reaction flask, stir at 50°C for 5 hours, cool the reaction to room temperature, filter, and use petroleum Wash with ether (100ml), filter, and dry und...

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

No PUM Login to View More

Abstract

The invention discloses a preparation method of 2-methyl-4-amino-6-chloropyrimidine. 4, 6-dihydroxy-2-methylpyrimidine, phosphorus oxychloride, an ammoniation reagent and the like are used as raw materials and subjecting to a two-step reaction to obtain the target product 2-methyl-4-amino-6-chloropyrimidine. The method is simple and convenient to operate, the comprehensive yield is over 81 percent, and compared with the existing yield of 68%, the yield is obviously increased, the production cost of the existing medicine is greatly reduced, and the method is suitable for industrial scale production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of 2-methyl-4-amino-6-chloropyrimidine. Background technique [0002] Dasatinib is a multityrosine kinase inhibitor, used for all stages of chronic myelogenous leukemia (chronic phase, accelerated phase, lymphoid cells) that have been treated, including imatinib mesylate resistance or intolerance adult patients with blast phase and myeloid blast phase). [0003] 2-Methyl-4-amino-6-chloropyrimidine, the molecular formula is C 5 h 6 ClN 3 , with a density of 1.35g / cm 3 , the English name is 6-Chloro-2-methylpyrimidin-4-amine, which is an important intermediate of dasatinib. [0004] As described in the follow-up comparative examples 1 and 2, in the prior art, the yield of the synthesis process of 2-methyl-4-amino-6-chloropyrimidine is only 68%, the operation is complicated, the reaction is difficult, the yield is low, and it is economical. B...

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
IPC IPC(8): C07D239/42
CPCC07D239/42
Inventor 王治国宋艳红马秀娟田贝贝李世江李超李强李涛
Owner SHANGHAI ZAIQI BIO TECH
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com