反应详情

A mixture of 5-chloro-7-morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)-thiazolo[5,4-d]pyrimidine (500 mg, 1.22 mmol), 1,2-diaminobenzene (300 mg, 2.77 mmol), palladium acetate (80 mg, 0.36 mmol), BINAP (110 mg, 0.18 mmol) and cesium carbonate (600 mg, 1.84 mmol) in 1,4-dioxane (5 mL)) was purged with argon gas then subjected to microwave irradiation at 150° C. for 30 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (25 g), washed with MeOH before the desired product was eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:2 M NH3 in MeOH 100:0 to 99:1 to 98:2 to 97:3) to afford N1-(7-morpholino-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-5-yl)benzene-1,2-diamine as a white solid (283 mg, 48%). LCMS (Method H): RT=2.40 min, [M+H]+ 483.

1. customwas purged with argon gas
2. customirradiation at 150° C. for 30 min
3. washwashed with MeOH before the desired product
4. washwas eluted
5. customThe product was collected
6. concentrationconcentrated in vacuo
7. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:2 M NH3 in MeOH 100:0 to 99:1 to 98:2 to 97:3)