Cesium carbonate → (2,2-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)(5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methanone

Participants

Reaction Conditions

Reaction Steps

A mixture of (5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-yl)-(2,2-dimethyl-4-oxetan-3-ylpiperazin-1-yl)methanone (137 mg, 0.30 mmol), 2-ethylbenzimidazole (47 mg, 0.32 mmol), tris(dibenzylideneacetone)dipalladium (8 mg, 2.5 mol %), XPhos (13 mg, 10 mol %) and Cs2CO3 (140 mg, 0.43 mmol) in DMF (4 mL) was purged with argon then heated at 150° C. for 30 min in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 1-2%) followed by triturating with EtOAc affording 793 (22 mg, 13%). LCMS (method I): RT 3.79 min [M+H]+ 563.3. 1H NMR (CDCl3, 400 MHz): δ 8.07-8.03 (1 H, m), 7.76-7.75 (1 H, m), 7.30-7.29 (2 H, m), 4.72 (2 H, t, J=6.51 Hz), 4.62 (2 H, t, J=6.07 Hz), 4.40 (4 H, brd s), 4.07-4.06 (2 H, m), 3.89 (4 H, t, J=4.72 Hz), 3.53-3.52 (1 H, m), 3.36 (2 H, q, J=7.46 Hz), 2.47 (2 H, t, J=5.08 Hz), 2.25 (2 H, s), 1.56 (6 H, s), 1.44 (3 H, t, J=7.45 Hz)

Provenance & Evidence