反应详情

The title compound was produced in analogy with example 106, steps A-G. Thus, esterification of (S)-4-benzyloxycarbonylamino-2-hydroxy-butyric acid gave (S)-4-benzyloxycarbonylamino-2-hydroxy-butyric acid ethyl ester, which was reduced in step B, leading to ((S)-3,4-dihydroxy-butyl)-carbamic acid benzyl ester. Hydrogenation in step C led to (S)-4-amino-butane-1,2-diol, followed by reductive alkylation in step D, thus producing (S)-4-(2,2-dimethoxy-ethylamino)-butane-1,2-diol. This was coupled with 2-(3,4-dichloro-phenylamino)-propionic acid (intermediate 11) to 2-(3,4-dichloro-phenylamino)-N—((S)-3,4-dihydroxy-butyl)-N-(2,2-dimethoxy-ethyl)-propionamide in step E, followed by reductive cyclization in step F, leading to 4-(3,4-dichloro-phenyl)-1-((S)-3,4-dihydroxy-butyl)-3-methyl-piperazin-2-one. Finally, mesylation and intramolecular cyclization, followed by reaction with (S)-6-aza-spiro[2.5]octan-4-ol hydrochloride (intermediate 2) in step G afforded 4-(3,4-dichloro-phenyl)-1-[(S)-3-hydroxy-4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-3-methyl-piperazin-2-one. Light yellow foam, MS: 456.2 (M+H)+.