反应详情

To an ice-cooled solution (0° C.) consisting of 2-phenylpyrimidine-5-carboxylic acid (prepared according to WO 2007/041634 Al Example 1, 2.10 g, 10.5 mmol) in dichloromethane (40 mL) was added triphosgene (1.55 g, 5.25 mmol) and triethylamine (7.3 mL, 52.45 mmol). Upon addition of triethylamine a yellow precipitate formed in solution. After stirring for five minutes in the ice bath, N,O-dimtheylhydroxylamine hydrochloride (1.02 g, 10.5 mmol) was added and the solution was allowed to slowly warm to room temperature over 30 minutes. The reaction was complete after stirring for three hours at room temperature. The crude solution was filtered and washed with excess dichloromethane. The filtrate was concentrated under reduced pressure to afford an orange solid. The crude product was purified by flash silica column chromatography. Elution through a 40-g Silicylce® flash silica cartridge with 10-30% ethyl acetate in hexanes afforded the title intermediate as a colorless oil (1.85 g, 72% yield); Rf 0.48 with 1:1 v/v hexanes-ethyl acetate; 1H-NMR (400 MHz; CDCl3) δ 9.20 (s, 2H), 8.50 (dd, 2H), 7.55 (m, 3H), 3.62 (s, 3H), 3.42 (s, 3H); MS (APCI+) m/z 244.0 (M+1).

1. customformed in solution
2. additionwas added
3. filtrationThe crude solution was filtered
4. washwashed with excess dichloromethane
5. concentrationThe filtrate was concentrated under reduced pressure
6. customto afford an orange solid
7. customThe crude product was purified by flash silica column chromatography
8. washElution through a 40-g Silicylce® flash silica cartridge with 10-30% ethyl acetate in hexanes