4-CHLORO-6-MORPHOLIN-4-YLPYRIMIDIN-2-AMINE synthesis

Yield:339016-18-1 96%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide at 100; for 5 h;Inert atmosphere;

Steps:

Synthesis of 4-chloro-6-morpholinopyrimidin-2-amine (Intermediate 22)

To a stirred solution of 4,6-dichloropyrimidin-2-amine (90.0 g, 540 mmol) in DMF (300 mL), placed in a 3 neck round bottom flask, under N₂atmosphere at rt, was added morpholine (48.0 mL, 548 mmol) and DIPEA (147 mL, 820 mmol). The reaction mixture was refluxed at 100 °C for 5 h. The reaction mixture was cooled to room temperature, diluted with ice cold water (1.0 L), whereupon the product precipitated. The precipitated product was collected by filtration under vacuum, washed with MTBE (200 mL) and dried under vacuum to obtain Intermediate 22 (113 g, 96% yield) as a brown solid.MS (ESI + APCI; multimode): 215 [M + H]⁺.¹H NMR (400 MHz, DMSO-d6): δ: 6.53 (brs, 2H), 6.09 (s, 1H), 3.65 - 3.44 (m, 8H).

References:

WO2021/163727,2021,A1 Location in patent:Page/Page column 184; 185; 293; 294; 307