Benzyl ((3R,4R)-4-fluoropyrrolidin-3-yl)carbamate → benzyl ((3R,4R)-4-fluoro-1-(9-isopropyl-6-((1-methyl-1H-pyrazol-4-yl)amino)-9H-purin-2-yl)pyrrolidin-3-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

To the above solution of crude 2-fluoro-9-isopropyl-N-(1-methyl-1H-pyrazol-4-yl)-9H-purin-6-amine was added benzyl [(3R,4R)-4-fluoropyrrolidin-3-yl]carbamate (238 mg, 1 mmol). The resulting solution was heated at 100° C. (block temperature) and stirred for 14 hr. After cooling, the volatiles were removed and the residue was purified via flash chromatography (eluting with a gradient of 100% heptane to 100% ethyl acetate and then to 10% ammonia (7 N in methanol-90% ethyl acetate) to give the title compound as a light yellow solid (402 mg, 82% yield (over 2 steps)). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.62 (s, 1 H) 7.98 (s, 1 H) 7.91 (s, 1 H) 7.80 (d, J=5.75 Hz, 1 H) 7.71 (s, 1 H) 7.27-7.41 (m, 5 H) 4.98-5.30 (m, 3 H) 4.55-4.68 (m, 1 H) 4.16-4.34 (m, 1 H) 3.76-3.96 (m, 6 H) 3.64-3.71 (m, 1 H) 1.50 (d, J=6.72 Hz, 6 H). 19F NMR (376 MHz, DMSO-d6) δ ppm −178.93 (br. s., 1F). m/z (APCI+) for C24H28FN9O2 494.2 (M+H)+. Chiral purity was determined as below (using racemic sample to compare):

Provenance & Evidence