1,2-Dichloroethane → HCID 178482375, compound

Participants

Reaction Steps

To a solution of 4-(2-methylamino-pyrimidin-4-yloxy)-benzene-1,2-diamine (Step C, 300 mg, 1.3 mmol, 1.0 eq) in anhydrous CH3CN (20 mL) was added drop-wise a solution of 1-(2-chloro-5-isothiocyanato-benzyl)-4-methyl-piperazine (405 mg [residual imidazole present], 1.3 mmol, 1.0 eq) in anhydrous CH3CN (10 mL). The solution was stirred for 16 h at RT. EDC (250 mg, 1.3 mmol, 1.0 eq) was added and the reaction was heated to 80° C. and stirred for 2 h. The solvent was removed under reduced pressure and residue was dissolved in CH2Cl2/MeOH (50 mL). The organic solution was washed with H2O (25 mL), NaHCO3 (aq, 25 mL) and brine (25 mL). The aqueous layers were back extracted with CH2Cl2 and the combined organic layers were dried over MgSO4, filtered and concentrated. The crude was further purified by column chromatography (0-10% MeOH/CH2Cl2 with 1% NH4OH) followed by preparative TLC and finally reverse phase HPLC (5-100% H2O/CH3CN with 0.1% TFA) to yield [4-chloro-3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[5-(2-methylamino-pyrimidin-4-yloxy)-1H-benzimidazol-2-yl]-amine. MS m/z=479.2 (M+H)+; MW Calc'd for C24H27ClN8O: 478.20.

Provenance & Evidence