反应详情

The solution of 3-(3,3-dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carbonitrile (0.130 g, 0.5 mmol) (Example 20) in THF (2 mL) is added borane dimethyl sulfide complex (0.055 mL, 0.55 mmol) dropwise, and the resulting mixture is stirred at reflux for 30 min. The reaction mixture is concentrated in vacuo and the residue is redissolved in THF (2 mL) and 0.5 M hydrogen chloride in methanol (1.1 mL, 0.55 mmol) is added dropwise. The reaction mixture is stirred at ambient temperature for 1.5 h. The mixture is concentrated in vacuo and the residue is purified by semi-preparative reverse phase HPLC to give 4-(5-aminomethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one as a yellowish solid; MS (ESI) m/z 271.9 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (s, 3 H), 1.59 (s, 3 H), 4.55-4.74 (m, 2 H), 5.99 (s, 1 H), 7.67-7.76 (m, 3 H), 7.82 (td, J=7.6, 1.5 Hz, 1 H), 8.29 (dd, J=7.7, 1.4 Hz, 1H), 8.52 (br. s, 1 H)

1. temperatureat reflux for 30 min
2. concentrationThe reaction mixture is concentrated in vacuo
3. dissolutionthe residue is redissolved in THF (2 mL)
4. stirringThe reaction mixture is stirred at ambient temperature for 1.5 h
5. concentrationThe mixture is concentrated in vacuo
6. customthe residue is purified by semi-preparative reverse phase HPLC