反应详情

温度

70 °C

To a round-bottom flask charged with 5-bromo-3-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)pyridin-2-amine (Compound 1078, 3.832 g, 10 mmol), tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (Compound 1098, 4.150 g, 11.00 mmol) and DME (100 mL) was flushed with N2 for 20 min. An aqueous solution of sodium bicarbonate (25 mL of 1.2 M, 30.00 mmol) was added. Nitrogen flow was continued for another 40 min before the addition of PdCl2 dppf (731.7 mg, 1.00 mmol). The resulting suspension was heated at 70° C. for 15 hours, filtered though a layer of diatomaceous earth, and washed with brine. The volatiles were removed in vacuo to afford a residue, which was purified by silica gel chromatography, eluting with 20-100% EtOAc/hexanes to yield tert-butyl 4-(4-(6-amino-5-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (Compound 1103, 2.8 g, 50.6%) as yellow solid; ESMS (M+H)=554.

1. customwas flushed with N2 for 20 min
2. filtrationfiltered though a layer of diatomaceous earth
3. washwashed with brine
4. customThe volatiles were removed in vacuo
5. customto afford a residue, which
6. customwas purified by silica gel chromatography
7. washeluting with 20-100% EtOAc/hexanes