反应详情

N,N-diisopropylethylamine (0.532 mL, 3.05 mmol) was added to a solution of 6-bromo-4-(((3 aS,4R,5R,6aS)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide TFA salt from Step 2 of Example 59 (250 mg, 0.508 mmol), 2-hydroxyacetic acid (77 mg, 1.016 mmol) and (benzotriazol-1-yloxy)tris(dimethylamine)phosphonium hexafluorophosphate (449 mg, 1.016 mmol) in N,N-dimethylformamide (5 mL). After 1 h at room temperature, the mixture was diluted with saturated sodium bicarbonate (5 mL) and ethyl acetate (100 mL), washed with water, brine, dried (MgSO4) and concentrated to give the expected product (210 mg). This material was used in the next reaction without purification. 1H NMR (400 MHz, methanol-d4) δ ppm 8.13 (1 H, s), 7.63 (1 H, s), 7.03 (1 H, d, J=1.32 Hz), 4.83-4.96 (2 H, m), 4.06-4.36 (2 H, m), 3.43-3.75 (3 H, m), 3.04-3.10 (1 H, m), 2.80-2.85 (1 H, m), 2.41-2.58 (1 H, m), 1.60-1.94 (1 H, m), 1.39-1.56 (1 H, m), 1.08-1.20 (3 H, m), MS (ES+) m/z: 436.1, 438.2 (M+H).

1. washwashed with water, brine
2. dry with materialdried (MgSO4)
3. concentrationconcentrated