Process for the preparation of compounds useful as inhibitors of SGLT

摘要

The present invention is directed to a novel process for the preparation of compounds having inhibitory activity against sodium-dependent glucose transporter (SGLT) being present in the intestine or kidney.

主权项

1. A process for the preparation of a compound of formula (I) wherein Ring A and Ring B are one of the followings: (1) Ring A is an optionally substituted unsaturated monocyclic heterocyclic ring, and Ring B is an optionally substituted unsaturated monocyclic heterocyclic ring, an optionally substituted unsaturated fused heterobicyclic ring, or an optionally substituted benzene ring; or (2) Ring A is an optionally substituted benzene ring, and Ring B is an optionally substituted unsaturated monocyclic heterocyclic ring, or an optionally substituted unsaturated fused heterobicyclic ring wherein Y is linked to the heterocyclic ring of the fused heterobicyclic ring; or (3) Ring A is an optionally substituted unsaturated fused heterobicyclic ring, wherein the sugar moiety X-(sugar) and the moiety -Y-(Ring B) are both on the same heterocyclic ring of the fused heterobicyclic ring, and Ring B is an optionally substituted unsaturated monocyclic heterocyclic ring, an optionally substituted unsaturated fused heterobicyclic ring, or an optionally substituted benzene ring; X is a carbon atom; Y is —(CH2)n—; wherein n is 1 or 2; provided that in Ring A, X is part of an unsaturated bond; or a pharmaceutically acceptable salt thereof, or a prodrug thereof; comprising reacting a compound of formula (V) with a compound of formula (VI-S), in the presence of an alkyl lithium, wherein the alkyl lithium is selected from the group consisting of trimethylsilylmethyl lithium, 2,4,6-trimethylphenyl lithium and triethylsilylmethyl lithium; in an organic solvent, at a temperature in the range of from about 0° C. to about −78° C.; to yield the corresponding compound of formula (VII); and wherein the alkyl lithium is added to a mixture of the compound of formula (V) and the compound of formula (VI-S); reacting the compound of formula (VII) with BF3OEt2, in the presence of a trialkylsilane, in an organic solvent, to yield the corresponding compound of formula (VIII); reacting the compound of formula (VIII) with acetic anhydride or acetyl chloride, in the presence of an organic base, neat or in an organic solvent, to yield the corresponding compound of formula (IX); and de-protecting the compound of formula (IX), to yield the corresponding compound of formula (I).