反应详情

温度

0.5 °C

A 3-necked 2 L RBF equipped with an addition funnel, temperature probe and nitrogen inlet was charged with tert-butyl (3-((5-formyl-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate (50) (25.0 g, 69.4 mmol) and THF (400 mL). The mixture was cooled to 0.5° C. using an ice water bath. Methylmagnesium bromide (3.0 M in Et2O, 74.0 mL, 222 mmol) was added dropwise via an addition funnel over 35 min. The temperature was kept below 8° C. during the addition. The reaction mixture was stirred for 90 min at 0.5° C. and then saturated NH4Cl (aq.) was added slowly via an addition funnel while cooling in ice. The mixture was stirred for 1 h then extracted with EtOAc (2×300 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered and concentrated furnishing a yellow solid. The yellow solid was suspended in Et2O (ca. 200 mL), filtered, washed with additional Et2O (2×50 mL), and dried under vacuum overnight affording tert-butyl (3-((5-(1-hydroxyethyl)-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate (23.17 g, 61.5 mmol, 89% yield) as a light yellow solid. m/z (ESI, +ve ion) 377.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.34 (1H, s), 8.86 (1H, s), 8.07 (1H, s), 7.80 (1H, s), 7.32 (1H, dd, J=8.1, 1.1 Hz), 7.19 (1H, t, J=8.1 Hz), 6.95-7.07 (1H, m), 5.87 (1H, d, J=4.1 Hz), 4.93 (1H, dd, J=6.5, 4.3 Hz), 2.43 (3H, s), 1.47 (9H, s), 1.40 (3H, d, J=6.5 Hz).

1. customA 3-necked 2 L RBF equipped with an addition funnel
2. additionThe temperature was kept below 8° C. during the addition
3. temperaturewhile cooling in ice
4. stirringThe mixture was stirred for 1 h
5. extractionthen extracted with EtOAc (2×300 mL)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over anhydrous MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customfurnishing a yellow solid
11. filtrationfiltered
12. washwashed with additional Et2O (2×50 mL)
13. customdried under vacuum overnight