Production of asymmetric 4,6-bis(aryloxy)-pyrimidine derivatives comprises two stage reaction of 4,6-dichloro-pyrimidine with phenols using 1,4-diazabicyclo(2.2.2)octane in second reaction stage

摘要

Asymmetric 4,6-bis(aryloxy)-pyrimidine derivatives are produced from a 4,6-dichloropyrimidine by reaction in two stages with two different phenols and by using 2-40 mol% of 1,4-diazabicyclo(2.2.2)octane in each of the second reaction stage. Production of asymmetric 4,6-bis(aryloxy)-pyrimidine derivatives comprises: (1) reaction of a 4,6-dichloropyrimidine of formula (II) with a phenol of formula (III) and reaction of the resulting 4-chloro-6-aryloxy-pyrimidine with a phenol of formula (V) in the presence of 2-40 mol% of 1,4-diazabicyclo(2.2.2)octane (DABCO); or (2) reaction of (II) with (V) and reaction of the resulting 4-aryloxy-6-chloro-pyrimidine of formula (VI) with (III) in the presence of 2-40 mol.% of DABCO. All reactions are optionally carried out in a diluent and/or in the presence of a base. X = H, F, Cl or Br; Ar1 = aryl or heteroaryl (both optionally substituted); Ar2 = group of formula (i): L1-L5 = H, halo, CN, NO2, alkylcarbonyl, CHO, alkoxycarbonyl, CONH2, CONH(alkyl), CON(alkyl)2, or alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl (each optionally substituted with halo); or L5 = a group of formula (i)-(v); X = CH or N; X1 = O or S; X2 = O or NH; Y = CH3, FH2C or F2HC; Y1 = CH3 or FH2C; and asterisk = linkage to phenyl; provided that Ar1 and Ar2 are not the same.