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. Author manuscript; available in PMC: 2019 Feb 8.
Published in final edited form as: J Med Chem. 2018 Jan 5;61(3):1182–1203. doi: 10.1021/acs.jmedchem.7b01654

Scheme 1. Synthesis of pyrimidineaminesa.

Scheme 1

a Reagents and conditions: (a) 2a, 3,5-Cl2PhNH2, DMSO, 100 °C, 18 h (8); (b) 2a-c,f-h or 3g, aniline (3,5-Cl2PhNH2 or 3-Br-5-ClPhNH2 or 6), conc. HCl, EtOH, microwave (140 °C), 1.5 h (9, 10, 15, 16, 26, 32-34, 36, 37, 44, 45, 53, 54, 61-68, 72, 73, 89); (c) 2a,d,e,h or 3d-f,h, aniline (3,5-Cl2PhNH2 or 3-Br-5-ClPhNH2 or 5a or 6) conc. HCl, EtOH, reflux, 18 h (13, 14, 23-25, 27, 28, 38-43, 46-48, 52, 55, 60, 69-71); (d) 7 or 13 or 32 or 38, ArylB(OH)2, Pd(OAc)2, PPh3, Na2CO3, H2O/DME, 90 °C, 18 h (11, 35, 50, 91-109, 116-118); (e) 13, DIPEA, morpholine, CH3CN, microwave (140 °C), 2 h (12); (f) 3,5-Cl2PhNH2, 3a,c,i,j, conc. HCl, BuOH, microwave (185 °C), 4 h (18-20, 22); (g) 3,5-Cl2PhNH2, 3b, conc. HCl, MeOH/H2O (1/1), sealed tube, 100 °C, 18 h (21); (h) 4, 3,5-Cl2PhNH2, cat. Pd2(dba)3, BINAP, NaOtBu, toluene, 70 °C, 18 h; then 3N aq. NaOH, EtOH, reflux, 18 h (17); (i) 2h, 5b, Et3N, DMF, rt, 24 h (29); (j) 2a, 5c,d, DIPEA, CH3CN, microwave (140 °C), 2 h (30, 31); (k) 48, conc. H2SO4, MeOH, 4Å mol. sieves, reflux, 18 h (49); (l) 48, 3,5-Cl2PhNH2, EDI, py/DCM/DMF (0.4/1/1), rt, 18 h (51); (m) 32, heteroaryl boronic acid MIDA-ester, cat. Pd(OAc)2, PPh3, sodium triphosphate, dioxane/H2O) (4/1), 90 °C, 18 h (110-115).