反应详情

A solution of (5-fluoro-pyridine-2-yl)-hydrazine (21.7 g, 171 mmol), Intermediate 3a (31.5 g, 180 mmol) and DIPEA (44.7 mmol, 256 mmol) in DCM (350 mL) was stirred at RT for 4 days. Water (350 mL) was added, then the aqueous layer extracted with DCM (100 mL). The combined organic extracts were passed through a hydrophobic fit and concentrated under vacuum to leave a solid. Trituration with diethyl ether/pentane (1:4, 150 mL), and drying under vacuum at 50° C., gave Intermediate 3b (31.7 g, 70%, ˜90% purity). LCMS: Rt 2.58 min, m/z 289 [MH+]. 1H NMR (300 MHz, CDCl3): 1.29 (6H, d, J=7.0 Hz), 1.45-1.89 (6H, m), 4.26 (2H, apparent quin, J=6.5 Hz), 6.53 (1H, s), 6.65 (1H, br s), 6.77 (1H, dd, J=9.0, 3.6 Hz), 7.29-7.28 (1H, ddd, J=9.0, 8.0, 3.0), 8.02 (1H, d, J=2.9 Hz).

1. extractionthe aqueous layer extracted with DCM (100 mL)
2. concentrationconcentrated under vacuum
3. customto leave a solid
4. dry with materialTrituration with diethyl ether/pentane (1:4, 150 mL), and drying under vacuum at 50° C.