反应详情

温度

5 °C

To a 100 L reactor fitted with a caustic scrubber was added 2-methyltetrahydrofuran (44.0 L), 2-fluoro-N-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-9H-purin-6-amine (2.20 kg, 8.36 mol, 1.00 eq) and potassium phosphate tribasic (7.10 kg, 33.43 mol mmol, 4.00 eq). The resulting mixture was stirred at 5° C. and dimethyl sulfate (1.42 kg, 11.28 mol, 1.35 eq) was added and the resulting mixture was stirred at 5° C. for 1 hr. The reaction was warmed from 5° C. to 15° C. over 2 hr and then held at 15° C. for 20 hr. The reaction mixture was cooled to 5° C. and quenched with water (44.0 L) while maintaining the internal temperature below 10° C. The mixture was then heated at 50° C. for 2 hr and then cooled to 10° C. and granulated for 2 hr. The product was isolated by filtration and washed with water (11.0 L) and then with 2-methyltetrahydrofuran (11.0 L). The cake was dried under vacuum at 40° C. for 8 hr to give the title compound (1.99 kg, 7.18 mol, 86% yield) as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.23 (br. s., 1 H) 8.13 (br. s., 1 H) 7.67 (s, 1 H) 3.78 (s, 3 H)3.70 (s, 3 H) 3.69 (br. s., 3 H). m/z (APCI+) for C11H13FN7O 278.2 (M+H)+.

1. customTo a 100 L reactor fitted with a caustic scrubber
2. stirringthe resulting mixture was stirred at 5° C. for 1 hr
3. temperatureThe reaction was warmed from 5° C. to 15° C. over 2 hr
4. temperatureThe reaction mixture was cooled to 5° C.
5. customquenched with water (44.0 L)
6. temperaturewhile maintaining the internal temperature below 10° C
7. temperatureThe mixture was then heated at 50° C. for 2 hr
8. temperaturecooled to 10° C.
9. waitgranulated for 2 hr
10. customThe product was isolated by filtration
11. washwashed with water (11.0 L)
12. customThe cake was dried under vacuum at 40° C. for 8 hr