Sodium triacetoxyborohydride → 4-(8-((3-(3,3-difluoropyrrolidin-1-yl)azetidin-1-yl)methyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholine

Participants

Reaction Steps

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (100 mg, 0.26 mmol), 1-azetidin-3-yl-3,3-difluoropyrrolidine (46 mg, 0.28 mmol) and 4 Å powdered molecular sieves in DCE (6 mL) was stirred at room temperature for 2 h before the addition of sodium triacetoxyborohydride (108 mg, 0.52 mmol). The reaction mixture was stirred for 16 h then filtered through celite, washing with DCM. The organic phase was washed with brine and concentrated in vacuo. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%) affording 589 as an orange foam (97 mg, 69%). LCMS (method I): RT 2.74 min [M+H]+ 538.2 1H NMR (CDCl3, 300 MHz): δ 8.00 (m, 1 H), 7.75 (m, 1 H), 7.27 (m, 2 H), 4.42-4.27 (m, 4 H), 3.87-3.84 (m, 9 H), 3.54 (t, J=6.5 Hz, 2 H), 3.32-3.30 (m, 3 H), 3.19 (t, J=6.5 Hz, 2 H), 2.89 (t, J=13.1 Hz, 2 H), 2.70 (t, J=6.9 Hz, 2 H), 2.29-2.28 (m, 2 H) and 1.44 (t, J=7.5 Hz, 3 H)

Provenance & Evidence