反应详情

To a solution of 4-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl]-2-isopropyl-3-oxopiperazine-1-carboxylic acid tert-butyl ester (104 mg, 0.17 mmol) in DCM (3 mL) was added TFA (1 mL) and the resulting mixture stirred for 2 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%) affording 681 as an off-white solid (55 mg, 67%). LCMS (method I): RT 2.54 min, [M+H]+ 518.2. 1H NMR (CDCl3, 400 MHz): δ 8.00-8.00 (1 H, m), 7.76-7.76 (1 H, m), 7.32-7.22 (2 H, m), 4.95-4.79 (1 H, m), 4.35 (4 H, brd s), 3.90-3.82 (7 H, m), 3.47-3.45 (3 H, m), 3.35 (2 H, q, J=7.48 Hz), 3.23-3.22 (1 H, m), 3.02 (1 H, ddd, J=12.50, 11.03, 3.93 Hz), 2.57-2.56 (1 H, m), 1.44 (3 H, t, J=7.48 Hz), 1.21 (1 H, t, J=7.02 Hz), 1.04 (3 H, d, J=7.12 Hz), 0.93 (3 H, d, J=6.80 Hz)

1. washwas washed with MeOH/DCM
2. washthe product eluted with 2M NH3/MeOH
3. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%)