The present invention provides stereoselective processes for the preparation of compounds of formula (I)
wherein
P is phenyl, naphthyl, a 6-membered heteroaryl group containing one or two nitrogen atoms as ring members, or a 10-membered bicyclic heteroaryl group containing one or two nitrogen atoms as ring members, and wherein the phenyl, naphthyl and heteroaryl groups are optionally substituted;
R
1
is chlorodifluoromethyl or trifluoromethyl;
R
2
is optionally substituted aryl or optionally substituted heteroaryl;
n is 0 or 1;
including the process comprising
(a-i) reacting a compound of formula II
wherein P, R
1
and R
2
are as defined for the compound of formula I;
with nitromethane in the presence a chiral catalyst to give a compound of formula III
wherein P, R
1
and R
2
are as defined for the compound of formula I; and
(a-ii) reductively cyclising the compound of formula III to give the compound of formula I.
The invention also provides intermediates useful for processes for the synthesis of compounds of formula (I).
本发明提供了用于制备式(I)化合物的立体选择性过程,其中
P为苯基、
萘基、含有一个或两个氮原子作为环成员的6元杂芳基,或含有一个或两个氮原子作为环成员的10元双环杂芳基,其中苯基、
萘基和杂芳基可以选择性地被取代;
R1为
氯二
氟甲基或三
氟甲基;
R2为可以选择性取代的芳基或可以选择性取代的杂芳基;
n为0或1;
包括以下过程
(a-i)将式II化合物与
硝基甲烷在手性催化剂存在下反应,得到式III化合物;
其中P、R1和R2如式I化合物中所定义;
(a-ii)将式III化合物还原环化,得到式I化合物。
本发明还提供了用于合成式(I)化合物的过程的中间体。