Acetic Acid → ethyl 3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)amino)cyclobutyl)propanoate

Participants

Reaction Steps

A mixture of 9-((3aR,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-amine (2.04 g, 6.66 mmol) and ethyl 3-(3-oxocyclobutyl)propanoate (1.2 g, 7.0 mmol) in methanol (41 mL) was treated with acetic acid (0.37 mL, 6.5 mmol) at rt and the flask was evacuated and flushed with nitrogen (×3). The reaction mixture was treated at rt with sodium cyanoborohydride (1.0 g, 16 mmol), which afforded instant gas evolution and a nearly colorless, clear solution in a few minutes. The reaction mixture was stirred for 1 h at rt; HPLC/LC MS indicated starting material remained. At 1 h 20 min additional ethyl 3-(3-oxocyclobutyl)propanoate (0.50 g, 2.93 mmol) in MeOH (3 mL) was added. The reaction mixture was stirred for 30 min and treated with water (12 mL). The mixture was concentrated in vacuo and the residual aqueous layer was diluted with saturated aqueous sodium bicarbonate (40 mL, to pH 9) and extracted with CH2Cl2 (3×60 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo to afford the crude title compound as a white foam/very pale yellow oil, which was carried on without further purification: MS (ESI+) for C22H32N6O5 m/z 461.2 (M+H)+ and 483.1 (M+Na)+.

Provenance & Evidence