RWJ-26240, McN-5691

Chemical Name: N-[2-(3,4-Dimethoxyphenyl)ethyl]-5-methoxy-N,alpha-dimethyl-2-(phenylethynyl)benzenepropanamine hydrochloride
CAS No. 99254-96-3, 99254-95-2 (free base)
项目整合开发状态: Phase II
项目研究机构: Ortho-McNeil (Originator)
合成路线:The condensation of 3-methoxybenzaldehyde (I) with acetone (II) by means of NaOH gives 1-(3-methoxyphenyl)-1-buten-3-one (III),which is hydrogenated with H2 over Pd/C in methanol yielding 1-(3-methoxyphenyl)-3-butanone (IV).The iodination of (IV) with I2-silver acetate in acetic acid affords 1-(2-iodo-5-methoxyphenyl)-3-butanone (V),which is reductocondensed with methylamine and sodium cyanoborohydride in methanol giving 2-iodo-5-methoxy-N,alpha-dimethylphenylpropanamine (VI).The acylation of (VI) with 3,4-dimethoxyphenylacetyl chloride (VII) by means of triethylamine in dichloromethane yields the corresponding acetamide (VIII),which is reduced with borane-THF complex affording the corresponding tertiary amine (IX),which is finally condensed with phenylacetylene (X) by means of butyllithium in THF.
📌 参考资料/链接:
参考文献标题:Aralkyl(arylethynyl)aralkyl amines for use as vasodilators and antihypertensives
文献作者:Carson,J.R.(McNeilab,Inc.)
参考来源:EP 0146271; ES 8604488; US 4661635

📄 详细内容


合成路线:The condensation of 3-methoxybenzaldehyde (I) with acetone (II) by means of NaOH gives 1-(3-methoxyphenyl)-1-buten-3-one (III),which is hydrogenated with H2 over Pd/C in methanol yielding 1-(3-methoxyphenyl)-3-butanone (IV).The iodination of (IV) with I2-silver acetate in acetic acid affords 1-(2-iodo-5-methoxyphenyl)-3-butanone (V),which is reductocondensed with methylamine and sodium cyanoborohydride in methanol giving 2-iodo-5-methoxy-N,alpha-dimethylphenylpropanamine (VI).The acylation of (VI) with 3,4-dimethoxyphenylacetyl chloride (VII) by means of triethylamine in dichloromethane yields the corresponding acetamide (VIII),which is reduced with borane-THF complex affording the corresponding tertiary amine (IX),which is finally condensed with phenylacetylene (X) by means of butyllithium in THF.

参考文献标题:McN-5691
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1989,14(4),322


合成路线:The condensation of 3-methoxybenzaldehyde (I) with acetone (II) by means of NaOH gives 1-(3-methoxyphenyl)-1-buten-3-one (III),which is hydrogenated with H2 over Pd/C in methanol yielding 1-(3-methoxyphenyl)-3-butanone (IV).The iodination of (IV) with I2-silver acetate in acetic acid affords 1-(2-iodo-5-methoxyphenyl)-3-butanone (V),which is reductocondensed with methylamine and sodium cyanoborohydride in methanol giving 2-iodo-5-methoxy-N,alpha-dimethylphenylpropanamine (VI).The acylation of (VI) with 3,4-dimethoxyphenylacetyl chloride (VII) by means of triethylamine in dichloromethane yields the corresponding acetamide (VIII),which is reduced with borane-THF complex affording the corresponding tertiary amine (IX),which is finally condensed with phenylacetylene (X) by means of butyllithium in THF.
参考文献标题:2-Ethynylbenzenealkanamines.A new class of calcium entry blockers
文献作者:Carson,J.R.; Almond,H.R.; Brannan,M.D.; et al.
参考来源:J Med Chem 1988,31(3),630-6


产品链接: CAS No.99254-95-2››