反应详情

温度

80 °C

Ethyl 4-((R)-(4-fluorophenyl)(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinate, 18-f, (7 g, 14 mmol) was dissolved in 50 ml of dioxane and treated with 5 ml of 3N NaOH. The mixture was heated at 80° C. for one hour. Then the mixture was concentrated under vacuum. The residue was diluted with water and washed with ethyl acetate. The aqueous layer was acidified with conc. HCl to pH=1 and the expected product crashed out (9.2 g of crude). The product can be further purified via prep-HPLC give 4 g of title product, 18-1, (Y=61%). 1H NMR (300 MHz, DMSO-d6): δ 10.32 (br, 1H), 8.62 (s, 1H), 8.43 (s, 1H), 8.05 (s, 1H), 7.46 (m, 2H), 7.37 (m, 4H), 7.20 (m, 2H), 6.72 (s, 1H), 6.33 (d, 1H), 1.50 (d, 3H). (M+H)+=468.1.

1. concentrationThen the mixture was concentrated under vacuum
2. additionThe residue was diluted with water
3. washwashed with ethyl acetate
4. customThe product can be further purified