3-Isocyanatopyridine → N-((1S,2R,3S,4R)-4-[6-(2,2-Diphenyl-ethylamino)-2-[(R)-3-(3-pyridin-3-yl-ureido)-pyrrolidin-1-yl]-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-2-hydroxy-acetamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-{(1S,2R,3S,4R)-4-[2-((R)-3-amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-2-hydroxy-acetamide trifluoroacetate (0.2 g, 0.28 mmol) in dry THF (10 ml) is treated with TEA (113 mg, 1.12 mmol) followed by 3-isocyanato-pyridine (38 mg, 0.31 mmol). The reaction mixture is heated at 50° C. overnight. The solvent is removed in vacuo and purification by reverse phase column chromatography (Isolute™ C18, 10-50% acetonitrile in water—0.1% TFA) affords the product. The product is further purified by dissolving in MeOH and treating with saturated sodium bicarbonate solution. The mixture is passed through a pre-washed (400 ml MeOH followed by 400 ml water) eluting with 0.5% ammonia 880: water (100 ml) followed by water (400 ml) and finally MeOH to afford the title compound. (MH+ 693.4)

Provenance & Evidence