公开(公告)号：EP1051397B1

公开(公告)日：2008-12-31

申请号：EP99904421.7

申请日：1999-01-29

申请人： Aventis Pharmaceuticals Inc.

发明人： HULME, Christopher ,  MORTON, George, C. ,  SALVINO, Joseph, M. ,  LABAUDINIERE, Richard, F. ,  MASON, Helen, J. ,  MORRISSETTE, Matthew, M. ,  MA, Liang ,  CHERRIER, Marie-Pierre

IPC分类号： C07D205/00 ,  C07D205/08 ,  C07D243/12 ,  C07D243/24 ,  C07D241/04 ,  C07D241/36 ,  C07D231/00 ,  C07D233/22 ,  C07D207/00 ,  C07D207/12 ,  C07D401/00 ,  C07D241/08

CPC分类号： C07D207/273 ,  C07C231/14 ,  C07C269/06 ,  C07C2601/02 ,  C07C2601/16 ,  C07D231/12 ,  C07D233/28 ,  C07D233/56 ,  C07D233/64 ,  C07D241/18 ,  C07D241/44 ,  C07D243/24 ,  C07D249/08 ,  C07D401/04 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D409/06 ,  C07F9/645 ,  C40B40/00 ,  Y02P20/55 ,  C07C237/22 ,  C07C271/28

摘要： The present invention relates to a method for preparing an N-[(aliphatic or aromatic)carbonyl]-2-aminoacetamide compound of formula (I) wherein Ra is (II); Raa is hydrogen, optionally substituted aliphatic or optionally substituted aromatic; Rb is hydrogen, optionally substituted aliphatic or optionally substituted aromatic; Rca and Rcb are independently hydrogen, optionally substituted aliphatic or optionally substituted aromatic; Rd is (III); and Rda is optionally substituted aliphatic or optionally substituted aromatic; and Raa is substituted with a primary or secondary protected amine that upon deprotection can react with the *ab or *db carbon, or at least one of Rb, Rca or Rcb where each is at least substituted with an activated carboxylic acid to form a 5-7 membered cyclic ring; or Rb is substituted with a primary or secondary protected amine that upon deprotection can react with the *ab or *db carbon, or at least one of Raa, Rca or Rcb where each is at least substituted with an activated carboxylic acid to form a 5-7 membered cyclic ring; or Rca and Rcb are independently substituted with a primary or secondary protected amine that upon deprotection can react with the *ab or *db carbon, or at least one of Raa, Rb, Rca, Rcb or Rda where each is at least substituted with an activated carboxylic acid to form a 5-7 membered cyclic ring; or Rda is substituted with a primary or secondary protected amine that upon deprotection can react with at least one of Rca or Rcb where each is at least substituted with an activated carboxylic acid to form a 5-7 membered cyclic ring, provided that when Raa is substituted with a primary or secondary protected amine that upon deprotection can react with Rb at least substituted with an activated carboxylic acid, then Raa is other than substituted aliphatic, comprising reacting the following four compounds: a carbonyl compound of formula (IV), an amine compound of formula NH2Rb, an isonitrile compound of formula NCRda, and an acid compound of formula RaCO2H, to produce the N-[(aliphatic or aromatic)carbonyl]-2-aminoacetamide compound, and the N-[(aliphatic or aromatic)carbonyl]-2-aminoacetamide compound. The invention is also directed to a method for cyclizing N-[(aliphatic or aromatic)carbonyl]-2-aminoacetamide compound to a cyclic compound selected from the group consisting of a 1,4-benzodiazepine-2,5-dione derivative, diketopiperazine derivative, ketopiperazine derivative, lactam derivative, 1,4-benzodiazapine derivative and dihydroquinoxalinones derivative, and the cyclized compound.

摘要翻译： 本发明涉及一种用于N个制备 - [（脂肪族或芳香族）羰基]式（I）-2-氨基乙酰胺化合物worin R a是（II）; RAA是氢，任选取代的脂或任选取代的芳族的; R b是氢，任选取代的脂或任选取代的芳族的; RCA和RCB是unabhängig氢，任选substituiertem脂肪族或芳香族OPTIONALLY substituiertem; R d是（III）; 和RDA任选substituiertem脂肪族或芳香族OPTIONALLY substituiertem; 和拉加与伯或仲保护的胺取代的并在去保护后能够与* AB或*分贝碳反应，或R b，RCA或RCB，其中每个是至少substituiertem与活化的羧酸，以形成一个5中的至少一个 -7元环; 或R b与伯或仲保护的胺取代的在去保护并可以通过* AB或*分贝碳反应，或拉加，RCA或RCB，其中每个是至少substituiertem与活化的羧酸，以形成一个5中的至少一个 -7元环; 或RCA和RCB是unabhängigsubstituiertem与伯或仲保护的胺并在去保护后能够与* AB或*分贝碳反应，或拉加，RB，RCA，RCB或RDA中的至少一个，其中每个是至少substituiertem与 活化的羧酸形成5-7元环; 或RDA是用伯或仲胺保护基取代并在去保护后能够与RCA或RCB中的至少一个，其中每个是至少substituiertem与活化的羧酸，以形成5-7元环状环反应，提供并当拉加是 与伯或仲胺保护时substituiertem脱保护确实可以与RB反应至少substituiertem与活化的羧酸，然后拉加比substituiertem脂肪族其他方法，包括将下列四种化合物：式的羰基化合物（IV）为胺 式NH2Rb的化合物，以异腈式NCRda的化合物，并在式RaCO2H的酸化合物，以产生N - [（脂肪族或芳香族）羰基] -2-氨基乙酰胺化合物，以及N - [（脂肪族或芳香族）羰基 ] -2-氨基乙酰胺化合物。 因此，本发明涉及用于环化N A方法 - [（脂肪族或芳香族）羰基] -2-氨基乙酰胺化合物由1,4-苯并二氮杂-2,5-二酮衍生物，二酮哌嗪从组中选择的环式化合物 衍生物，ketopiperazine衍生物，内酰胺衍生物，1,4-苯二氮衍生物和dihydroquinoxalinones衍生物，环化化合物。