反应详情

A solution of ethyl 5-amino-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylate (200 mg, 0.861 mmol) and 1-chloropyrrolidine-2,5-dione (172 mg, 1.292 mmol) in dichloromethane (8 mL) was added tert-butyl nitrite (0.154 mL, 1.292 mmol). The reaction mixture was stirred at rt for 30 minutes, after which time it was concentrated to yield a crude product which was purified on a silica gel column eluting with hexanes/EtOAc to yield ethyl 5-chloro-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylate. The material from Method 1 and Method 2 were combined (106 mg, 0.42 mmol). HPLC ret. time=2.50 min. HPLC: Column: YMC S5 COMBISCREEN® 4.6×50 mm; Gradient time: 4 min; Flow rate=4 mL/min; Solvent A=10% MeOH—90% Water—0.2% H3PO4; Solvent B=90% MeOH—10% water—0.2% H3PO4; Start % B=0; Final % B=100. LC-MS: M+1=252.1. 1H NMR (400 MHz, MeOD) δ ppm 8.61 (1 H, dd, J=4.89, 1.13 Hz), 8.16 (1 H, s), 8.09 (1 H, td, J=7.78, 1.76 Hz), 7.74 (1 H, d, J=8.03 Hz), 7.57 (1 H, ddd, J=7.53, 4.77, 1.00 Hz), 4.36 (2 H, q, J=7.28 Hz), 1.38 (3 H, t, J=7.15 Hz).

1. concentrationafter which time it was concentrated
2. customto yield a crude product which
3. customwas purified on a silica gel column
4. washeluting with hexanes/EtOAc