MC-1220

Chemical Name: 6-[1-(2,6-Difluorophenyl)ethyl]-2-(dimethylamino)-5-methylpyrimidin-4(3H)-one
CAS No. 391681-51-9
项目整合开发状态: Preclinical
项目研究机构: Idenix (Originator), Universit?degli Studi "La Sapienza" (Originator), Universit?degli Studi di Cagliari (Originator)
合成路线:The condensation of 2-(2,6-difluorophenyl)acetic acid (I) with lmalonic acid monoethyl ester sodium salt (II) gives 4-(2,6-difluorophenyl)--3-oxobutyric acid ethyl ester (III),which is cyclized with thiourea (IV) to yield 6-(2,6-difluorobenzyl)-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (V).Finally this compound is reacted with cyclopentyl chloride (VI) by means of K2CO3 to afford the target pyrimidinone.

合成路线:The condensation of 2-(2,6-difluorophenyl)acetic acid (I) with 2-methylmalonic acid monoethyl ester sodium salt (II) gives 4-(2,6-difluorophenyl)-2-methyl-3-oxobutyric acid ethyl ester (III),which is cyclized with thiourea (IV) to yield 6-(2,6-difluorobenzyl)-5-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (V).Finally this compound is reacted with cyclopentyl chloride (VI) by means of K2CO3 to afford the target pyrimidinone.

合成路线:The alkylation of 6-(2,6-difluorobenzyl)-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (I) with cyclopentyl chloride (II) by means of K2CO3 gives 2-(cyclopentylsulfanyl)-6-(2,6-difluorobenzyl)pyridmidin-4(3H)-one (III),which is then methylated with Me-Cl and LDA in THF/HMPA to yield the target alpha-methylbenzyl pyrimidinone.

合成路线:The methylation of 2-(2,6-difluorophenyl)acetic acid (I) with Me-Cl and LDA in THF/HMPA gives 2-(2,6-difluorophenyl)propionic acid (II),which is condensed with malonic acid monoethyl ester potassium salt (III) to yield 4?2,6-difluorophenyl)-3-oxopentanoic acid (IV).The cyclization of (IV) with thiourea (V) affords 6-[1-(2,6-difluorophenyl)ethyl]-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (VI),which is finally alkylated with cyclopentyl chloride (VII) to provide the target pyrimidinone derivative.

合成路线:The alkylation of 6-(2,6-difluorobenzyl)-5-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (I) with cyclopentyl chloride (II) by means of K2CO3 gives 2-(cyclopentylsulfanyl)-6-(2,6-difluorobenzyl)-5-methylpyridmidin-4(3H)-one (III),which is then methylated with Me-Cl and LDA in THF/HMPA to yield the target alpha-methylbenzyl pyrimidinone.

合成路线:The methylation of 2-(2,6-difluorophenyl)acetic acid (I) with Me-Cl and LDA in THF/HMPA gives 2-(2,6-difluorophenyl)propionic acid (II),which is condensed with 2-methylmalonic acid monoethyl ester potassium salt (III) to yield 4?2,6-difluorophenyl)-2-methyl-3-oxopentanoic acid (IV).The cyclization of (IV) with thiourea (V) affords 6-[1-(2,6-difluorophenyl)ethyl]-5-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (VI),which is finally alkylated with cyclopentyl chloride (VII) to provide the target pyrimidinone derivative.