145525-41-3

Kissei (Japan)

Mitiglinide Calcium is a blood glucose-lowering drugs, stimulating insulin secretion by closing the ATP-sensitive K+ channels in pancreatic beta-cells

ChEBI: Kad 1229 is a polymer.

Glufast

A number of publications and patents have disclosed the syntheses of mitiglinide. One of the syntheses describing the preparation of mitiglinide using bis-activated esters to obtain a selective mono amide is described in Scheme 8. The synthesis starts with racemic 2-benzylsuccinic acid (51) which was resolved into its enantiomer using chiral amine salt formation and crystallization. Out of several amines used, (R)-1- phenylethylamine gave the best results for the chiral resolution (99.5% ee, 19.5%). Acid 52 was treated with thionyl chloride and triethylamine followed by Nhydroxysuccinamide to give doubly activated ester 53 (97%). Treatment of this double ester 53 with tetrahydroisoindoline (54) gave selectively mono amide to di-amide in 99:1 ratio. Hydrolysis of the activated ester in 55 with water gave desired product 56 in 99% yield. Subsequent conversion in two steps to the half calcium salt provided mitiglinide calcium hydrate (VIII) in 91% yield.