4-Pyrimidinamine, 5,6-dimethyl- (9CI)

Synthesis

General procedure for the synthesis of 5,6-dimethylpyrimidin-4-amine from 4-chloro-5,6-dimethylpyrimidine: to a solution of 4-chloro-5,6-dimethylpyrimidine (0.18 g, 1.26 mmol) in anhydrous toluene (4 mL) was added sequentially sodium tert-butoxide (0.17 g, 1.77 mmol), Pd2(dba)3 (0.12 g, 0.13 mmol), BINAP (0.24 g, 0.38 mmol) and benzophenone imine (0.25 mL, 1.51 mmol). The reaction mixture was degassed (by three evacuation/nitrogen-filling cycles) and subsequently heated to 80 °C and stirred for 1 hour. Upon completion of the reaction, the mixture was cooled to room temperature, diluted with ether (100 mL) and filtered through a pad of diatomaceous earth. The filtrate was concentrated under reduced pressure and the resulting oil was dissolved in tetrahydrofuran (20 mL) and 3 M aqueous hydrochloric acid (0.63 mL, 1.89 mmol) was added. The mixture was stirred at room temperature for 3 h. The mixture was subsequently concentrated under reduced pressure, neutralized with saturated aqueous sodium bicarbonate solution and diluted with dichloromethane (50 mL). The aqueous phase was back-extracted with dichloromethane (2 x 50 mL). The organic phases were combined, separated by phase separation tubing and concentrated. The residual orange solid was ground several times with ether and dried to afford the target product 5,6-dimethylpyrimidin-4-amine (0.067 g, 0.54 mmol, 42% yield). The product was characterized by 1H NMR (400 MHz, CDCl3): δ 8.38 (s, 1H), 4.78 (bs, 1H), 2.43 (s, 3H), 2.08 (s, 3H).

References

[1] Patent: WO2009/3997, 2009, A1. Location in patent: Page/Page column 21
[2] Chemische Berichte, 1901, vol. 34, p. 2813