反应详情

A mixture of [(S)-1-((R)-1-piperidin-3-yl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine from Example 16 (150 mg, 0.414 mmol), dimethylaminoacetic acid (47 mg, 0.455 mmol), HOAt (62 mg, 0.455 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (87 mL, 0.455 mmol) and 4-methylmorpholine (0.10 mL, 0.911 mmol) in anhydrous DCM (4 mL) was stirred at RT for 20 h. Volatiles were removed in vacuo and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM) then triturated with diethyl ether affording 134 (55 mg, 30%). LCMS: RT 1.79 min [M+H]+ 448.1. 1H NMR (DMSO, 400 MHz): δ 8.23-7.93 (3H, m), 7.90-7.78 (1H, m), 7.68-7.58 (1H, m), 7.21-7.12 (2H, m), 4.80-4.69 (1H, br), 4.53-4.30 (1H, m), 4.22 (0.6H, bd, J=12.25 Hz), 4.03 (0.4H, bd, J=12.25 Hz), 3.85 (0.6H, t, J=12.08 Hz), 3.44-3.26 (1.4H, t, J=12.08 Hz), 3.21-3.10 (1H, m), 2.99 (0.4H, bd, J=13.04 Hz), 2.90-2.64 (1.6H, m), 2.44-2.26 (1H, m), 2.25-2.11 (6H, m), 1.85-1.58 (5H, m), 1.13-0.97 (1H, m). Signals split due to presence of rotamers

1. customVolatiles were removed in vacuo
2. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM)
3. customthen triturated with diethyl ether affording 134 (55 mg, 30%)
4. customSignals split due to presence of rotamers