4-Iodo-1-tritylimidazole → 2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine

Temperature

70 °C

To a solution of 4-Iodo-1-trityl-1H-imidazole (Synthonix, 2.0 g, 4.58 mmol) in THF (50 mL) at room temperature was added ethylmagnesium bromide (Aldrich, 1.0 M solution in THF, 5.5 mL, 5.50 mmol) under dry conditions. After stirring for 90 minutes, zinc chloride (Aldrich, 0.749. g, 5.50 mmol) was added to the reaction mixture. After stirring for an additional 90 minutes, tetrakis(triphenyl)phosphine)palladium (Strem, 0.529 g, 0.46 mmol) and 5-bromo-2-phenylpyrimidine (as prepared in Example 1, step A, 1.29 g, 5.50 mmol) were added to the reaction mixture. The reaction mixture was heated in a 70° C. oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with 0.5 M EDTA buffer (at pH ˜9) (2×250 mL) followed by brine (150 mL). The organics were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash silica column chromatography using an 80 g Silicycle® column (elution with 10-30% ethyl acetate in hexane) which afforded the desired intermediate, 2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine, as a white solid (1.38 g, 65%). Rf 0.87 with 95:5 v/v dichloromethane-methanol; 1H-NMR (400 MHz; DMSO-d6) δ 9.29 (s, 2H), 8.42 (m, 2H), 7.92 (d, 1H), 7.62 (d, 1H), 7.56-7.43 (m, 13H), 7.24-7.22 (m, 6H); MS (ESI−) m/z 463.0 (M−1); H-PGDS FPBA IC50: >20 μM.

1. stirringAfter stirring for an additional 90 minutes
2. temperatureUpon cooling
3. washwashed with 0.5 M EDTA buffer (at pH ˜9) (2×250 mL)
4. dry with materialThe organics were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude product was purified by flash silica column chromatography
8. washan 80 g Silicycle® column (elution with 10-30% ethyl acetate in hexane) which

ORD record

ord-4efe0042766d459ab4f9c536c728c18f

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536185B2