Preparation method for optically active diamino derivative

Abstract

The invention provides an optically active diamino derivative, and intermediates and a preparation method thereof. The intermediates comprise intermediates F1 and F with a (1R,2R,5S) configuration; and the optically active diamino derivative is a compound with a (1R,2S,5S) configuration and as shown in a formula H. F1, F and H are described in the specification. In F1, F and H, R1 is an alkyl amino-protecting group or an aryl amino-protecting group, e.g., a benzyl group, an alkyl-substituted benzyl group, an alkoxy-substituted benzyl group, an alkoxycarbonyl group or a benzyloxycarbonyl group;R2 is an alkoxycarbonyl, alkyl or aryl amino-protecting group, e.g., a tertbutyloxycarbonyl group, a benzyloxycarbonyl group or a methoxycarbonyl group; X is a hydroxyl group, halogen, OMs, OTf or OTs; R is an alkoxy group or as described in the specification; and R3 is an amino group protected by an amide amino-protecting group, imine groups such as phthalimido, succinimido or naphthalimido groups, diphenyl azidophosphate, -N3, an amino group or a substituted amino group.

Description

technical field [0001] The invention relates to the field of pharmaceutical synthesis, in particular to optically active diamino derivatives, intermediates and preparation methods thereof. Background technique [0002] Compounds with the following structure of formula L-1 or formula L-2 are optically active diamino derivatives, and are intermediates for the synthesis of edoxaban: [0003] [0004] Chinese patent application CN103080078A (applicant: Daiichi Sankyo Co., Ltd.) discloses the salt of the optically active diamino derivative with the same structure. And in its instruction manual [0010] section, disclose the reaction equation that this compound involves in chemical formula 3: [0005] [0006] As disclosed in the patent application, this process exists that when compound 2 is azide, the trans isomer of compound 3 will be formed, and then when reduced, the trans isomer will also be reduced to form 1a-trans Mode. In order to solve this problem, referred to as...

AI Technical Summary

Problems solved by technology

However, there is another problem in this route, that is, due to the presence of active hydrogen on the NH connected to the tert-butoxycarbonyl group in the azidation reaction, an impurity with the following structure will be formed:

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