反应详情

温度

80 °C

A solution of 2-imidazol-1-yl-4-methyl-6-pyrrolidin-2-yl-pyrimidine (2.1 g, 9.2 mmol) in DMF (15 mL) was added all at once to a stirred mixture of benzo[1,3]dioxol-5-ylmethyl-(2-chloro-ethyl)-methyl-amine hydrochloride salt (2.2 g, 8.1 mmol), DMF (10 mL) and diisopropylethylamine (2.5 mL) at ambient temperature under nitrogen. A catalytic amount of potassium iodide (340 mg, 2.0 mmol) is then added. The mixture is heated to 80° C. for 3 h. The solution is then cooled to room temperature, quenched into 200 mL of 1N dibasic potassium phosphate solution (pH 9), and extracted with ethyl acetate. The combined organics are dried over MgSO4, filtered and concentrated to a red residue. Purification via silica gel column chromatography (DCM to 4:1 DCM/MeOH) gave 2.0 g (52%) of benzo[1,3]dioxol-5-ylmethyl-{2-[2-(2-imidazol-1-yl-6-methyl-pyrimidin-4-yl)-pyrrolidin-1-yl]-ethyl}-amine as a red oil. [M+H]+ 421.30; 1H-NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 7.89 (s, 1H), 7.30 (s, 1H), 7.10 (s, 1H), 6.78 (s, 1H), 6.67 (m, 2 H), 5.88 (s, 2H), 3.52 (t, 1H, J=6.8 Hz), 3.6 (m, 3H), 2.77 (m, 1H), 2.2-2.6 (m, 8H), 1.62-1.95 (m, 3H). 13C-NMR (100 MHz, CDCl3) δ 175.7, 169.6, 154.0, 147.6, 146.5, 136.2, 132.8, 130.1, 121.9, 116.6, 115.0, 109.2, 107.8, 100.8, 69.8, 62.3, 56.0, 54.3, 53.1, 42.5, 33.2, 24.2, 23.4.

1. temperatureThe solution is then cooled to room temperature
2. customquenched into 200 mL of 1N dibasic potassium phosphate solution (pH 9)
3. extractionextracted with ethyl acetate
4. dry with materialThe combined organics are dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated to a red residue
7. customPurification via silica gel column chromatography (DCM to 4:1 DCM/MeOH)