反应详情

Into a 50-mL round-bottom flask, was placed a solution of 4-(1-(3-(2-(azetidin-3-yl)-4-methyl-1H-imidazol-5-yl)-4-methylbenzoyl)azetidin-3-yl)benzonitrile (compound 189.2, 50 mg, 0.12 mmol) in tetrahydrofuran (1 mL). Formaldehyde (65 μL, 37% wt, 0.57 mmol) and NaBH3CN (30 mg, 0.48 mmol) were added to the reaction. The reaction mixture was stirred for 1 h at room temperature. The reaction mixture was extracted with 3×3 mL of ethyl acetate and the combined organic extracts were washed with 3×1 mL of brine and concentrated under reduced pressure. The crude product (20 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020): Column, XBridge Prep C18 OBD Column, 5 μm, 19*150 mm; mobile phase, WATER WITH 0.03% NH3H2O and MeCN (26.0% MeCN up to 40.0% in 7 min, up to 100.0% in 2 min, down to 26.0% in 1 min); Detector, Waters 2489, 254 and 220 nm. This resulted in 1.8 mg (3%) of the title compound as a white solid. m/z (ES+) 426 (M+H)+.

1. customInto a 50-mL round-bottom flask, was placed
2. extractionThe reaction mixture was extracted with 3×3 mL of ethyl acetate
3. washthe combined organic extracts were washed with 3×1 mL of brine
4. concentrationconcentrated under reduced pressure
5. customThe crude product (20 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020)
6. waitmobile phase, WATER WITH 0.03% NH3H2O and MeCN (26.0% MeCN up to 40.0% in 7 min
7. waitup to 100.0% in 2 min
8. waitdown to 26.0% in 1 min)