J-106366

Chemical Name: 2(R)-Cyclopentyl-2-hydroxy-N-[1-[4(S)-methylhexyl]piperidin-4-yl]-2-phenylacetamide
项目整合开发状态: Preclinical
项目研究机构: Banyu (Originator)
合成路线:The chiral precursor (IV) was obtained by two alternative procedures.Addition of cyclopentylmagnesium bromide (II) to ethyl phenylglyoxylate (I) afforded the racemic hydroxyester (III).Basic hydrolysis of the ethyl ester group of (III) gave the corresponding carboxylic acid,which was resolved using cinchonidine.

合成路线:An alternative asymmetric procedure consisted in the LDA-promoted addition of cyclopentenone (VI) to the chiral dioxolanone (V),followed by catalytic hydrogenation to furnish (VII).The dioxolane group of (VII) was then cleaved by basic hydrolysis yielding the target (R)-hydroxyacid (IV).

合成路线:The alkylation of 4-(tert-butoxycarbonylamino)piperidine (VIII) with (S)-4- methylhexyl methanesulfonate (IX) provided the tertiary amine (X).Cleavage of the Boc protecting group of (X) gave aminopiperidine (XI),which was finally coupled with the chiral hydroxyacid (IV) by means of carbonyl diimidazole.

合成路线:The chiral precursor (IV) was obtained by two alternative procedures.Addition of cyclopentylmagnesium bromide (II) to ethyl phenylglyoxylate (I) afforded the racemic hydroxyester (III).Basic hydrolysis of the ethyl ester group of (III) gave the corresponding carboxylic acid,which was resolved using cinchonidine.

合成路线:An alternative asymmetric procedure consisted in the LDA-promoted addition of cyclopentenone (VI) to the chiral dioxolanone (V),followed by catalytic hydrogenation to furnish (VII).The dioxolane group of (VII) was then cleaved by basic hydrolysis yielding the target (R)-hydroxyacid (IV).

合成路线:The alkylation of 4-(tert-butoxycarbonylamino)piperidine (VIII) with 5-bromo-2-methyl-2-pentene (IX) provided the tertiary amine (X).Cleavage of the Boc protecting group of (X) gave aminopiperidine (XI),which was finally coupled with the chiral hydroxyacid (IV) by means of carbonyl diimidazole.