The Enantiospecific Synthesis of an Isoxazoline. A RGD Mimic Platelet GPIIb/IIIa Antagonist

Abstract

A convergent, large-scale, chiral synthesis of isoxazoline 1 has been achieved in 37% overall yield and >99.6% optical purity, starting from L-asparagine and 4-cyanobenzaldehyde. Hofmann reaction of N(alpha)-n-Boc-L-asparagine with iodosobenzene diacetate provides optically pure N(alpha)-n-Boc-L-alpha,beta-diaminopropionic acid (8) in 75% yield. A process of lipase resolution-base catalyzed epimerization gives the single enantiomer 5. Reaction of acid 5 with amine 9 in the presence of thionyl chloride forms the framework of 1. A Pinner reaction of intermediate 4 in methyl acetate or anisole, followed by an amidination with ammonium acetate, gives optically pure product 1.

Efficient Preparation of Aldoximes from Arylaldehydes, Ethylenediamine and Oxone® in Water

“…All of the products except for 3g were known compounds and their structures were confirmed by comparison of their melting points, 1 H-and 13 C-NMR and IR spectra with reported data [5,[14][15][16][17][18]. The use of other amines replacing ethylenediamine was studied under the same conditions.…”

Carbon‐13 and carbon‐14 labeled dabigatran etexilate and tritium labeled dabigatran

“…Ester hydrolysis to [ 13 C 6 ]‐( 6 ), activation with carbonyldiimidazole (CDI) followed by condensation with ( 7 ) gave [ 13 C 6 ]‐( 8 ) in 76% yield over three steps. Pinner reaction followed by treatment of the resulting ethylamidate with ammonium carbonate gave [ 13 C 6 ]‐( 9 ) in 69% yield. Reaction with n ‐hexyl chloroformate ( 10 ) in acetone gave [ 13 C 6 ]‐dabigatran etexilate [ 13 C 6 ]‐( 11 ) in 38% yield after silica gel chromatography purification.…”

Amino acid chlorides: a journey from instability and racemization toward broader utility in organic synthesis including peptides and their mimetics

“…1). [45][46][47][48][49][50][51] The harsh conditions including elevated temperatures employed during acid chloride preparation using PCl 5 or SOCl 2 leads to side reactions. The isolation of pure products in case of reagents PCl 5 , POCl 3 is also cumbersome.…”