反应详情

Solid tert-butyl 4-(4-(2-phenylpyrimidin-5-yl)-1H-imidazol-2-yl)piperidine-1-carboxylate (Example 17, 122 mg, 0.30 mmol) was treated with trifluoroacetic acid 2.0 mL) at room temperature for 15 minutes. Three times the reaction mixture was diluted with toluene and concentrated under reduced pressure to provide a dark semi-solid. The crude material was chromatographed on silica (12 g) eluted with 1:5:85 v/v acetic acid-methanol-dichloromethane. Some clean fractions were collected, concentrated, and the purified material was three times diluted with toluene and concentrated then promoted to solidify under hexane with scratching to afford the title compound (19 mg) as a light-pink acetate salt. The remaining fractions were collected, concentrated, three times diluted with toluene and concentrated to afford a semi-solid; Rf 0.17 with 1/10/90 v/v acetic acid/methanol/dichloromethane; 1H-NMR (400 MHz; DMSO-d6) δ 9.20 (s, 2H), 8.6-8.8 (br d, 1H), 8.3-8.5 (m, 3H), 7.83 (s, 1H), 7.45-7.55 (m, 3H), 3.2-3.5 (m, 2H), 2.95-3.2 (m, 3H), 2.1-2.2 (m, 2H), 1.8-2.0 (m, 5H); MS (ESI+) m/z 306 (M+1); H-PGDS FPBA IC50: 1 μM.

1. concentrationconcentrated under reduced pressure
2. customto provide a dark semi-solid
3. customThe crude material was chromatographed on silica (12 g)
4. washeluted with 1:5:85 v/v acetic acid-methanol-dichloromethane
5. customSome clean fractions were collected
6. concentrationconcentrated
7. additiondiluted with toluene
8. concentrationconcentrated