SKEAD, Ben,WESTWOOD, Robert,LONDESBROUGH, Derek,NORTHERN, Julian,ATHERTON, Chris
申请号：
GBGB2018/050208
公开号：
WO2018/138500A1
申请日:
2018.01.25
申请国别(地区):
GB
年份:
2018
代理人:
摘要：
The present invention relates to a process for preparing a compound of formula [I], said process comprising the steps of: formula [II]+formula [III]−>；formula [I] (i) forming a reaction mixture comprising (a) a compound of formula [II], (b) a compound of formula [III] and (c) 1,2-propanediol or polyethylene glycol, or a mixture thereof, and optionally (d) a base； (ii) heating said reaction mixture to a temperature of at least about 150°C to form a compound of formula [I]； (iii) isolating said compound of formula [I]； and (iv) optionally converting said compound of formula [I] into salt form； wherein: R1 and R2 are each independently H, alkyl or haloalkyl； R3 and R4 are each independently H, alkyl, haloalkyl or aryl； R5 is alkyl, alkenyl, cycloalkyl or cycloalkyl-alkyl, each of which may be optionally substituted with one or more OH groups； R6 is selected from cyclopropylamino, cyclopropylmethylamino, cyclobutylamino, cyclobutylmethylamino and formula (A) where one of X, Y and Z is N and the remainder are CR9； R7, R8 and each R9 are independently H, alkyl or haloalkyl, wherein at least one of R7, R8 and R9 is other than H. Further aspects of the invention relate to a highly diastereoselective process for the preparation of compounds of formula [III], a process for preparing intermediates of formula [II], and other intermediates useful in the synthesis of compounds of formula [I], and to a process for preparing the crystalline tartrate salt and free base of compounds of formula [I].La présente invention concerne un procédé de préparation d'un composé de formule [I], ledit procédé comprenant les étapes consistant à : formule [II] + formule [III] −>； formule [I] (i) former un mélange réactionnel comprenant (a) un composé de formule [II], (b) un composé de formule [III] et (c) du 1,2-propanédiol ou du polyéthylène glycol, ou un mélange de ceux-ci, et éventuellement (d) une base ； (ii) chauffer ledit mélange réactionnel à une température d'au moins environ 150 °C pour
