Scheme 1
Synthesis of N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)piperidine-4-carboxamide and its analogs. Reagents and conditions: (i) 100 °C; (ii) NaOH, n-butanol, 110 °C; (iii) SnCl2·2H2O, hydrochloric acid, 0 °C-r.t.; (iv) IBCF, NMP, DMF; (v) MDC, TEA, 0 °C-r.t. 9a = 4-nitrobenzene sulfonyl chloride; 9b = 2-methylbenzene sulfonyl chloride; 9c = 4-methoxybenzene sulfonyl chloride; 9d = 3-chlorobenzene sulfonyl chloride; 9e = 3,4-difluorobenzene sulfonyl chloride; 9f = 2,6-difluorobenzene sulfonyl chloride; (vi) MDC, TEA, 0 0C-r.t. 11a = 4-chlorobenzoyl chloride; 11b = 4-fluorobenzoyl chloride; 11c = 4-(trifluoromethyl)benzoyl chloride; (vii) MDC, TEA, 0 0C-r.t; 13a = 4-chlorophenyl isothiocyanate; 13b = 2-methoxyphenyl isothiocyanate; 13c = 3-methoxyphenyl isothiocyanate