BUHR, CHRIS A,LARA, KATHERINE,MA, SUNGHOON,MAC, MORRISON,NUSS, JOHN M,WANG, LONGCHENG,WANG, YONG,YEUNG, BRYAN K S,BAIK, TAE-GON
申请号：
NZ59462806
公开号：
NZ594628A
申请日:
2006.10.09
申请国别(地区):
NZ
年份:
2013
代理人:
摘要：
Disclosed herein is a process for the preparation of compounds of formula (I), wherein the substituents are as defined within the specification, comprising: Reacting an intermediate of formula 7(a) with an intermediate of formula R2NH2 to yield a compound of formula I(a)； or Reacting an intermediate of formula 18 with tributyl-1-ethylvinyltin or with an intermediate of formula R6B(OH)2 to yield a compound of formula I(a) or I(b)； or Reacting an intermediate of formula 25(a) with an intermediate of R2NH2 to yield a compound of formula I(a)； and Optionally further resolving individual isomers； and optionally further modifying one of the R1, R2, R4 and R6 groups. Particularly preferred is the preparation of 2-amino-8-ethyl-4-methyl-6(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one, comprising: Coupling 6-bromo-8-ethyl-4-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one with 1Hpyrazol-5-ylboronic acid in the presence of a palladium catalyst, to afford 8-ethyl-4-methyl-2-(methylthio)-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one； Treatment of the product obtained in step a) with an oxidizing agent and subsequently ammonia to provide 2-amino-8-ethyl-4-methyl-6(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one. Also disclosed are intermediates useful in the process of preparing compounds of formula (I), namely: 8-ethyl-4-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)one； 6-bromo-8-ethyl-4-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one； N-ethyl-5-iodo-6-methyl-2-(methylthio)pyrimin-4-amine； N-ethyl-6-methyl-2-(methylthio)pyrimidin-4-amine； and (E)-ethyl-3-(4-(ethylamino)-6-methyl-2-(methylthio)pyrimidin-5-yl)acrylate.
