Sodium hydride → 5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine

反応式

[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.[H-].[Na+].[NH2:12][C:13]1[C:18]([F:19])=[CH:17][N:16]=[C:15](Cl)[N:14]=1>O1CCOCC1>[F:19][C:18]1[C:13]([NH2:12])=[N:14][C:15]([O:7][CH2:6][C:5]2[CH:8]=[CH:9][C:2]([F:1])=[CH:3][CH:4]=2)=[N:16][CH:17]=1

参加物

実験手順

To a solution of 4-fluorobenzyl alcohol (2.56 g, 20.3 mmol) in 1,4-dioxane (20 mL) was added 60% NaH (0.813 g, 20.3 mmol) in several portions over a period of 10 min. To the magnetically stirred solution was added 4-amino-2-chloro-5-fluoropyrimidine* (2.00 g, 13.6 mmol) and the mixture was stirred at room temperature until gas evolution subsided. The reaction mixture was then heated in a CEM Discover microwave reactor at 120° C. for 90 min. The cooled reaction mixture was partitioned between ethyl acetate and water, the organic phase was concentrated, and the product was purified by column chromatography (hexane/ethyl acetate gradient) to yield 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine (1.66 g, 52% yield) as a white solid: mp 129-131° C.; 1H NMR (300 MHz, CDCl3) δ 7.91 (d, J=2.6 Hz, 1H), 7.42 (m, 2H), 7.03 (m, 2H), 5.27 (s, 2H), 5.05 (br s, 2H); MS (ESI) m/z 238 (M+H)+. *4-Amino-2-chloro-5-fluoropyrimidine can be purchased commercially or can be prepared through known literature methods. 1. Hayashi, T.; Kawakami, T. JP Patent 2005126389 2. Durr, G. J. J. Med. Chem. 1965, 8(2), 253.