2-Amino-4-chloro-6-methylpyrimidine → N4,6-Dimethyl-N4-[(8-methyl-2-phenylquinolin-3-yl)methyl]pyrimidine-2,4-diamine

Participants

Reaction Steps

A mixture of 8-methyl-2-phenylquinoline-3-carboxaldehyde (100 mg, 0.4 mmol), methylamine hydrochloride (120 mg, 1.8 mmol) and DIPEA (230 mg, 1.8 mmol) in DCM (20 mL) was treated with titanium(IV) n-propoxide (228 mg, 0.8 mmol). The reaction mixture was stirred at r.t. for 18 h. The solvent was removed in vacuo and the residue dissolved in THF (20 mL) before triacetoxyborohydride (170 mg, 0.8 mmol) was added. The reaction mixture was stirred at r.t. for 2 h, the solvent removed in vacuo and the residue partitioned between DCM (100 mL) and water (30 mL). The organic layer was separated, dried (MgSO4) and the solvent removed in vacuo. The residue was dissolved in NMP (2 mL) and to this solution was added DIPEA (230 mg, 1.8 mmol) and 2-amino-4-chloro-6-methylpyrimidine (57 mg, 0.4 mmol). The mixture was heated in a microwave at 220° C. for 2 h. Purification by preparative HPLC (Method 1) gave the title compound as an off-white solid (30 mg, 20%). δH (CDCl3) 7.82 (s, 1H), 7.62-7.70 (m, 2H), 7.61 (d, J 7.9 Hz, 1H), 7.46-7.55 (m, 5H), 5.75 (s, 1H), 4.93 (s, 2H), 4.67 (s, 2H), 2.93 (s, 3H), 2.82 (s, 3H), 2.22 (s, 3H). LCMS (ES+) 370.2 (M+H)+, RT 2.36 minutes (Method 3).

Provenance & Evidence