Cesium carbonate → 4-(6-((2,2-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)methyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-chloro-6-(2,2-dimethyl-4-oxetan-3-ylpiperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (136 mg, 0.31 mmol), 2-ethylbenzimidazole (48 mg, 0.33 mmol), tris(dibenzylideneacetone)dipalladium (8 mg, 3 mol %), XPhos (14 mg, 9 mol %) and Cs2CO3 (143 mg, 0.44 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, 0-5%) then (Si—PCC, 2M NH3/MeOH:DCM, 0-2%) affording 792 as a cream solid (45 mg, 26%). LCMS (method I): RT 2.78 min [M+H]+ 548.3. 1H NMR (CDCl3, 400 MHz): δ 7.97-7.96 (1 H, m), 7.75-7.74 (1 H, m), 7.32-7.22 (3 H, m), 4.66 (2 H, t, J=6.47 Hz), 4.59 (2 H, t, J=6.08 Hz), 4.04 (4 H, t, J=4.72 Hz), 3.91-3.86 (6 H, m), 3.46-3.45 (1 H, m), 3.33 (2 H, q, J=7.48 Hz), 2.64 (2 H, t, J=4.98 Hz), 2.33 (2 H, s), 2.14 (2 H, s), 1.42 (3 H, t, J=7.47 Hz), 1.20 (6 H, s)

Provenance & Evidence