Yield:4894-86-4 12%

Reaction Conditions:

Stage #1: isopropanolwith sodium hydride in tetrahydrofuran;mineral oil at 0 - 25; for 1 h;
Stage #2: 2-chloropyrimidin-4-ylamine in tetrahydrofuran;mineral oil at 60; for 12 h;

Steps:

I.1 Step 1: 2-Isopropoxypyrimidin-4-amine

Sodium hydride (60% dispersion in oil, 617 mg, 15.4 mmol, 2.00 equiv) was added to a mixture of propan-2-ol (696 mg, 11.6 mmol, 1.50 equiv) in tetrahydrofuran (10 mL) at 0 °C. The mixture was stirred at 25 °C for 1 h, 2-chloropyrimidin-4-amine (1.00 g, 7.72 mmol) was added and the mixture was heated to 60 °C. After stirring for 12 h, the reaction mixture was cooled to ambient temperature and quenched by addition of water (20 mL). The quenched mixture was extracted with EA (20 mL × 3), and the layers were combined. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a residue. The residue was purified by reverse phase prep- HPLC (column: Xtimate C18150*25mm*5um; mobile phase: [water (0.05% ammonia hydroxide v/v)-MECN]; B%: 0%-30%,10min) to give the title compound (140 mg, 12% yield) as a white solid. ¹H-NMR (400 MHz, DMSO-d6): δ ppm 7.93 (d, J = 6.0 Hz, 1H), 7.37 (s, 2H), 6.38 (d, J = 6.0 Hz, 1H), 5.08 (td, J = 6.4, 12.3 Hz, 1H), 1.22 (d, J = 6.0 Hz, 6H).

References:

WO2021/146370,2021,A1 Location in patent:Page/Page column 148; 149