MS-28168

Chemical Name: (-)-2-[6-[4-(4-Morpholinylcarbonimidoyl)benzamido]-3,4-dihydro-2H-1-benzopyran-3(S)-yl]acetic acid hydrochloride
CAS No. 188350-52-9, 188349-94-2 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Mitsui Chemicals (Originator)
合成路线:Nitration of chromanone (I) with fuming HNO3 at -35 C afforded 6-nitro-4-chromanone (II).Subsequent aldol condensation of (II) with glyoxylic acid (III) in the presence of H2SO4 produced the alpha-beta-unsaturated acid (IV).Further hydrogenation of the nitro,keto,and olefin groups of (IV) with concomitant esterification produced the benzopyranylacetate (V).After protection of (V) as the N-Boc derivative (VI),optical resolution was achieved by preparative HPLC on a Chiralcel-OD column.The desired (S)-enantiomer (VI) was deprotected using ethanolic HCl to afford amine (VII),which was condensed with 4-cyanobenzoyl chloride (VIII) to give amide (IX).Treatment of (IX) with HCl-EtOH produced imidate (X),and subsequent treatment with morpholine (XI) furnished the target amidine,which was isolated as the hydrochloride salt.

合成路线:Nitration of chromanone (I) with fuming HNO3 at -35 C afforded 6-nitro-4-chromanone (II).Subsequent aldol condensation of (II) with glyoxylic acid (III) in the presence of H2SO4 produced the alpha-beta-unsaturated acid (IV).Further hydrogenation of the nitro,keto,and olefin groups of (IV) with concomitant esterification produced the benzopyranylacetate (V).After protection of (V) as the N-Boc derivative (VI),optical resolution was achieved by preparative HPLC on a Chiralcel-OD column.The desired (S)-enantiomer (VI) was deprotected using ethanolic HCl to afford amine (VII),which was condensed with 4-cyanobenzoyl chloride (VIII) to give amide (IX).Treatment of (IX) with HCl-EtOH produced imidate (X),and subsequent treatment with morpholine (XI) furnished amidine (XII).Finally,basic hydrolysis of the ester function provided the target amidinoacid,which was isolated as the hydrochloride salt.