4-Pyrimidinamine, 5-methoxy- (9CI) Chemical Properties

Melting point:

118.5-119.0 °C

Boiling point:

264.3±20.0 °C(Predicted)

Density 

1.224±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

pka

5.04±0.10(Predicted)

Appearance

Off-white to light yellow Solid

4-Pyrimidinamine, 5-methoxy- (9CI) Usage And Synthesis

Synthesis

General procedure for the synthesis of 4-amino-5-methoxypyrimidines from 4-chloro-5-methoxypyrimidines: 4-chloro-5-methoxypyrimidines (I-89) (40 g, 280 mmol) was suspended in NH3(g)/EtOH (4 M, 2000 mL), the suspension was transferred to an autoclave, and the reaction was stirred for 12 hours at 130 °C. The progress of the reaction was monitored by TLC (unfolding agent: CH2Cl2/MeOH = 10:1) and after confirming the completion of the reaction, the reaction mixture was cooled to room temperature. Subsequently, the mixture was concentrated under vacuum to obtain the residue. CH2Cl2 (100 mL) was added to the residue and stirred at room temperature for 30 minutes. The reaction mixture was filtered to remove the NH4Cl salt and the filtrate was concentrated under vacuum to give the crude product. The crude product was stirred with a solvent mixture of EtOAc/CH2Cl2 (50 mL, 4:1) for 30 min, filtered and concentrated in vacuum to give the final 4-amino-5-methoxypyrimidine (I-90) (30 g, 87% yield) as a yellow solid. The structure of the product was confirmed by 1H NMR (400 MHz, DMSO-d6): δ 8.01 (s, 1H), 7.81 (s, 1H), 6.75 (br.s., 2H), 3.81 (s, 3H).

References

[1] Patent: WO2016/97918, 2016, A1. Location in patent: Page/Page column 80
[2] Organic Process Research and Development, 2015, vol. 19, # 6, p. 639 - 645
[3] European Journal of Medicinal Chemistry, 2009, vol. 44, # 10, p. 4179 - 4191