反应详情

A solution of amine 5 was titrated with chloroacetyl chloride with monitoring by TLC (SiO2/8:1 and 14:1 DCM:MeOH) as follows: Neat chloroacetyl chloride (0.45 mL; 5.7 mmol) was slowly added down the side of a flask immersed in an ice-water bath into a solution of aminopyrimidine 5 (1.531 g; 5.64 mmol) and 2,6-lutidine (2.0 mL; 17 mmol) in DCM (30 mL) plus DMF (2.5 mL). Starting material remained so additional chloroacetyl chloride was added after 0.4 h (0.45 μL; 5.7 mmol) and again after an additional 0.5 h (90 IL; 1.1 mmol). After 0.5 h, EtOAc (150 mL) was added and the solution washed with saturated NaHCO3 (40 mL), 50% saturated NaCl (5×40 mL), saturated NaCl (2×40 mL), dried (MgSO4), filtered and concentrated to a yellow-orange crystalline solid. The crude material was triturated with hexanes (10 mL) then 1:1 hexanes:Et2O (2×10 mL) then purified on silica gel (250 mL) with 18:1 DCM:MeOH yielding a hard yellow foam (1.78 g; 91%). LC (method B) tR=13.5 min; 1H NMR (200 MHz, CDCl3) δ 8.70 (brs, 1H), 8.35 (m, 2H), 7.47 (m, 3H), 7.16 (s, 1H), 6.48 (brs, 1H), 5.59 (brt, 1H), 4.19 (s, 2H), 3.68 (m, 2H), 3.54 (m, 2H), 1.88 (s, 3H); ESIMS 347.9/349.9 (100/32) [MH+].

1. additionwas added after 0.4 h (0.45 μL; 5.7 mmol)
2. waitAfter 0.5 h
3. washthe solution washed with saturated NaHCO3 (40 mL), 50% saturated NaCl (5×40 mL), saturated NaCl (2×40 mL)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated to a yellow-orange crystalline solid
7. customThe crude material was triturated with hexanes (10 mL)
8. custom1:1 hexanes:Et2O (2×10 mL) then purified on silica gel (250 mL) with 18:1 DCM