Intermediates of sitagliptin and preparation process thereof

摘要

Disclosed are intermediates of Sitagliptin, a preparation process thereof, and a process for synthesizing Sitagliptin using these intermediates. Sitagliptin is synthesized by using chiral amino compounds as a raw material, without having to build a chiral center with a chiral asymmetric catalytic hydrogenation, and high-pressure hydrogenation is avoided.

主权项

1. An aziridine compound (I) with absolute configuration R represented by Formula I: wherein: R1 is —CH2SR3, wherein R3 is C1-C4 alkyl; or R1 is —CH2OR4, wherein R4 is selected from the group consisting of methyl, substituted methyl, tetrahydropyranyl, methoxyphenyl, ethyl, benzyl, substituted benzyl and silyl;
wherein the substituted methyl is selected from the group consisting of methoxymethyl, methylthiomethyl, benzyloxymethyl, (p-methoxybenzyloxy)methyl, 2-methoxyethoxymethyl, and 2-trimethylsilylethoxymethyl;the substituted benzyl is selected from the group consisting of p-methoxybenzyl, 3,4-dimethoxybenzyl and p-nitrobenzyl; andthe silyl is selected from the group consisting of trimethylsilyl, triethylsilyl, tri-isopropylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, diphenylmethylsilyl and tert-butylmethoxyphenylsilyl; andR2 is selected from the group consisting of hydrogen, formate group, acyl, sulfonyl, benzyl and 4-methoxybenzyl;wherein the formate group is selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, 9-fluorenylmethoxycarbonyl, 2-chloro-3-indenylmethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-trimethylsilylethoxycarbonyl, homobenzyloxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl and allyloxycarbonyl;the acyl is selected from the group consisting of formyl, acetyl, trifluoroacetyl and benzoyl; andthe sulfonyl is trifluoromethylsulfonyl.