反应详情

温度

150 °C

A mixture of (5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-yl)-(3-morpholin-4-ylazetidin-1-yl)methanone (98 mg, 0.23 mmol), 2-ethylbenzimidazole (36 mg, 0.25 mmol), tris(dibenzylideneacetone)dipalladium (6 mg, 2.5 mol %), XPhos (10 mg, 9 mol %) and Cs2CO3 (107 mg, 0.33 mmol) in DMF (3 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:EtOAc, 0-4%) then triturated with EtOAc affording 846 as a white solid (61 mg, 50%). LCMS (method I): RT 2.96 min, [M+H]+ 535.3. 1H NMR (CDCl3, 400 MHz): δ 8.09-8.05 (1 H, m), 7.80-7.75 (1 H, m), 7.31-7.30 (2 H, m), 4.68-4.67 (1 H, m), 4.60-4.20 (4 H, brd s), 4.52 (1 H, dd, J=10.01, 5.05 Hz), 4.33-4.27 (1 H, m), 4.17 (1 H, dd, J=10.73, 5.02 Hz), 3.89 (4 H, t, J=4.65 Hz), 3.78 (4 H, t, J=4.57 Hz), 3.42-3.33 (3 H, m), 2.52-2.35 (4 H, m), 1.46 (3 H, t, J=7.44 Hz)

1. customwas purged with argon
2. washwas washed with MeOH
3. washthe product eluted with 2M NH3/MeOH
4. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-4%)
5. customthen triturated with EtOAc affording 846 as a white solid (61 mg, 50%)
6. customRT 2.96 min, [M+H]+ 535.3