3-Butyn-1-OL → 2-(but-3-yn-1-yloxy)-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]ethanone

Participants

Reaction Conditions

Reaction Steps

To sodium hydride (60 wt % in mineral oil, 2.06 g, 51.4 mmol) in tetrahydrofuran (86 mL) at 0° C., add 3-butyn-1-ol (4.64 g, 5.03 mL, 64.3 mmol), then stir at 23° C. for 15 minutes. Add this solution to 2-chloro-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]ethanone (8.45 g, 25.7 mmol) in tetrahydrofuran (86 mL) at 0° C. and stir for five minutes. Pour reaction mixture into 50% saturated aqueous sodium bicarbonate solution. Separate the organic layer and further extract the aqueous layer with ethyl ether and ethyl acetate (2×50 mL each). Combine the organic extracts and wash with brine, then dry over anhydrous sodium sulfate, filter, and concentrate. Combine the crude product with the crude product from a second reaction (run reaction under identical conditions and stoichiometry employing 2-chloro-1-[2-(indan-2-ylamino)-5,7-dihydropyrrolo[3,4-d]pyrimidin-6-yl]ethanone (3.0 g, 9.1 mmol)) and purify by silica gel column chromatography (gradient elution: 25% ethyl acetate in hexanes to 100% ethyl acetate) to give the title compound (2.90 g, 23%). MS (m/z): 363(M+1).

Provenance & Evidence