Novel Processes and Intermediates

• Main Authors: DEVRIES KEITH MICHAEL, HOOVER DENNIS JAY, HANMEN PHILIP DIETRICH, JORGENSEN JEFFERY BRIAN, FOX DARRELL EUGENE
• Format: Patent
• Language: English; Korean
• Published: 15.06.2001
• Edition: 7
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; APPARATUS THEREFOR; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

PURPOSE: Provided is a novel manufacturing method of 3(S)-((5-chloro-1H-indole-2-carbonyl)- amino)-2(R)-hydroxy-4-phenyl-butyric acid at a low cost by reacting two specific kinds of compounds and extracting with an organic solvent, thereby producing indole-2-carboxamide and its derivative which have an inhibition effect on glycogen phosphorylase and useful for the treatment glycogen phosphorylase related diseases. CONSTITUTION: The compound of formula(6) is produced by: reacting a compound of formula(5) in an aprotic solvent A in the presence of a catalytic solvent and an activation agent in an inert gas atmosphere to obtain a compound of formula(2); separately reacting a compound of formula(3) in the presence of a base, etc. in a liquid mixture of an aprotic solvent B and a protonic solvent at about pH 8-13 at the refluxing temperature to obtain a compound of formula(4); mixing a solution of the compound of formula(2) with a solution of the compound of formula(4) in an inert gas atmosphere while keeping the temperature; cooling the product to room temperature to obtain a compound of formula(5); separating the water layer A and the organic layer A; treating the organic layer A with an aqueous solution of an acid or the aqueous solution and H2O; separating the water layer B from the organic layer B; keeping the organic layer B; and extracting the objective compound of formula(6) to the organic solvent. 본 발명은 3(S)-[(5-클로로-1H-인돌-2-카르보닐)-아미노]-2(R)-히드록시-4-페닐-부티르산의 신규한 제조 방법에 관한 것이다. 또한, 상기 방법에 사용되는 신규한 중간체가 제공된다. 또한, 신규한 방법으로 제조된 3(S)-[(5-클로로-1H-인돌-2-카르보닐)-아미노]-2(R)-히드록시-4-페닐-부티르산을 추가 반응시켜 글리코겐 포스포릴아제에 따른 질환 또는 증상을 갖는 포유류, 특히 사람의 치료에 유용한 글리코겐 포스포릴아제 억제 활성을 갖는 공지된 인돌 2-카르복사미드 및 그의 유도체를 얻을 수 있다.