Diisopropylamine → tert-butyl 3-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylene)azetidine-1-carboxylate

Participants

Reaction Steps

To a solution of diisopropylamine (1.4 mL, 9.8 mmol) in THF (3 mL) at −78° C. was added n-BuLi (3.9 mL, 9.8 mmol, 2.5 M in hexanes) and the resulting mixture allowed to stir for 20 min. The resulting solution was added to a pale green solution of (2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl)phosphonic acid dimethyl ester (3.36 g, 8.9 mmol) in THF (80 mL) at −78° C. The resulting mixture was warmed to r.t. before a solution of 3-oxo-azetidine-1-carboxylic acid tert-butyl ester (1.76 g, 10.2 mmol) in THF (10 mL) was added. The resulting pink mixture was stirred for 16 h then quenched with H2O. The mixture was concentrated in vacuo and the residue was partitioned between DCM and brine. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-70%) affording the title compound as a green powder (3.46 g, 92%). 1H NMR (CDCl3, 400 MHz): δ 6.33-6.32 (1 H, m), 4.91-4.90 (2 H, m), 4.71-4.70 (2 H, m), 4.28 (4 H, brd s), 3.81 (4 H, t, J=4.74 Hz), 3.71 (3 H, s), 1.48 (9 H, s).

Provenance & Evidence