Dimethylformamide → HCID 178461917, compound

Participants

Reaction Conditions

Reaction Steps

[(S)-1-(7-Bromo-1-phenyl-1H-benzoimidazol-2-yl)ethyl][9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine (300 mg, 0.58 mmol) was dissolved in DMF (1 mL) in a microwave vial and zinc cyanide (68 mg, 0.58 mmol) and Pd(PPh3)4 (67 mg, 0.058 mmol) added. The vial was sealed and evacuated and purged with argon (×3). The vial was heated at 150° C. by microwave irradiation for 15 min. The resulting colourless solution was poured onto a mixture of EtOAc and water. A white solid precipitated and was dispersed between the 2 phases. The solid was isolated by filtration and dissolved in DCM and the resulting solution washed with NaHCO3 (satd. aq. soln.). The DCM fraction was passed through a PTFE cartridge. The DCM was removed in vacuo and the residue purified by passage through an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH. The product fractions were combined and evaporated and the residue purified by chromatography (Si—PCC) eluting with 0-8% MeOH in DCM. The product fractions were concentrated in vacuo to give white solid. This was triturated in ether, filtered and dried in vacuo to give 279 as a white solid (160 mg, 73%). 1H NMR (DMSO-d6, 400 MHz) δ: 8.09 (1H, br s), 8.03 (1H, s), 7.98 (2H, d, J=8.2 Hz), 7.66-7.59 (3H, m), 7.56-7.37 (4H, m), 7.33 (1H, t, J=7.9 Hz), 5.35-5.21 (1H, m), 1.54 (3H, d, J=6.9 Hz). LCMS (Method K): RT 3.07 min; m/z 381 [M+H]+

Provenance & Evidence