您的位置: 首页 > 农业专利 > 详情页

A novel method for the synthesis of ivabradine and its addition salts with pharmaceutically acceptable acids
专利权人:
レ ラボラトワール セルヴィエ
发明人:
ジャン-ルイ・ペリヨン,エメ・デサンジュ,ジャン-ルイ・ペリヨン
申请号:
JP2012028129
公开号:
JP5475813B2
申请日:
2012.02.13
申请国别(地区):
JP
年份:
2014
代理人:
摘要:
Preparing ivabradine (I) comprises: reductive amination of aldehyde compound (VI) with N'-[[(8S)-3,4-dimethoxy-8-bicyclo[4.2.0]octa-1(6),2,4-trienyl]methyl]-N'-methyl-propane-1,3-diamine (VII) in the presence of reducing agent to give (bicyclo[4.2.0]octatrienylmethyl)-propane-diamine compound (VIII); condensing (VIII) with (3,4-dimethoxy-phenyl)-acetyl chloride (IX) to give substituted phenyl-acetamide compound (X); cyclizing (X); and hydrogenating 3-{3-[((S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-methyl-amino]-propyl}-7,8-dimethoxy-1,3-dihydro-benzo[d]azepin-2-one (V). Preparing ivabradine (I) comprises: reductive amination reaction of aldehyde compound of formula (R2-CHR1-C(=O)-H) (VI) with N'-[[(8S)-3,4-dimethoxy-8-bicyclo[4.2.0]octa-1(6),2,4-trienyl]methyl]-N'-methyl-propane-1,3-diamine (VII) in the presence of a reducing agent, or organic solvent and its mixture or a mixture of organic solvent and water, to give (dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-methyl-propane-1,3-diamine compound of formula (VIII); condensing (VIII) with (3,4-dimethoxy-phenyl)-acetyl chloride (IX) in the presence of a base in an organic solvent, to give a substituted phenyl-acetamide compound of formula (X); cyclizing (X) in an acid medium to give 3-{3-[((S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-methyl-amino]-propyl}-7,8-dimethoxy-1,3-dihydro-benzo[d]azepin-2-one (V); and hydrogenating (V) to give ivabradine (I), which is optionally converted into its addition salts with an acid comprising hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, tartaric acid, maleic acid, citric acid, ascorbic acid, oxalic acid, methanesulfonic acid, benzenesulfonic acid and camphoric acid, and their hydrates. Either R1, R2 : 1-6C alkoxy groups; or CR1R2 : 1,3-dioxane, 1,3-dioxolane or 1,3-dioxepane. Independent cl
来源网站:
中国工程科技知识中心
来源网址:
http://www.ckcest.cn/home/

意 见 箱

匿名:登录

个人用户登录

找回密码

第三方账号登录

忘记密码

个人用户注册

必须为有效邮箱
6~16位数字与字母组合
6~16位数字与字母组合
请输入正确的手机号码

信息补充