[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C[N:9]([C:11]([O:15]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:32][CH2:33][N:34]([CH:38](C)C)[CH:35](C)[CH3:36].O>C1COCC1.C(Cl)Cl.C(OCC)(=O)C>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:11]([N:9]2[CH2:36][CH2:35][N:34]([CH3:38])[CH2:33][CH2:32]2)=[O:15])[CH2:4][CH2:3]1In THF (20 mL) were dissolved 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amine)pyrimidine-5-carboxylic acid (153 mg, 0.41 mmol), 1-methylpiperazine (49 mg, 0.49 mmol) and HATU (188 mg, 0.49 mmol). The solution was cooled in an ice bath then DIEA was added dropwisely (0.14 mL, 0.82 mmol). The reaction was conducted at ambient temperature for 8 h, followed by addition of water (20 mL) and extraction with ethyl acetate or DCM. The organic phase was dried, concentrated and purified by silica gel column chromatography (DCM/methanol=25/1) to give 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidin-5-yl)(4-methylpiperazin-1-yl)ketone (35 mg, 19% yield).
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