合成路线1

Oxidation of 2-fluoro-3-nitrotoluene (I) by means of CrO3 in the presence of H2SO4 in AcOH/H2O yields 2-fluoro-3-nitrobenzoic acid (II), which is converted to the methyl ester (III) by treatment with MeOH and H2SO4. Reduction of the nitro group in compound (III) with N2H4.H2O in the presence of Ra-Ni in THF/MeOH affords amine (IV), which then is coupled with 2,6-difluorobenzenesulfonyl chloride (V) using pyridine in CH2Cl2 to produce the benzenesulfonamide derivative (VI). Condensation of methyl ester (VI) with 2-chloro-4-methylpyrimidine (VII) by means of LiHMDS in THF gives diaryl ethanone (VIII), which by bromination with NBS in DMA or CH2Cl2, followed by cyclization of the crude bromo ketone with 2,2-dimethylpropanethioamide (IX) [prepared by thionation of pivalamide (X) with Lawesson’s reagent in refluxing THF], yields thiazole derivative (XI). Finally, 2-chloropyrimidine derivative (XI) is aminated with NH4OH in H2O/dioxane at 100 °C or with NH3 in MeOH at 90 °C in a sealed vessel, followed by treatment of the resulting free base with MsOH in i-PrOH/acetonitrile .
Alternative synthesis of amine (IV): Esterification of 3-bromo-2-fluorobenzoic acid (XII) with MeOH and H2SO4 provides methyl ester (XIII), which is then condensed with tert-butyl carbamate by means of Pd2(dba)3.CHCl3, xantphos and Cs2CO3, followed by Boc group cleavage with TFA in CH2Cl2 .