反应详情

To a solution of 4,6-dichloro-pyrimidine-5-carbonitrile (254 mg, 1.47 mmol) and 2,3-difluoroaniline (190 mg, 1.47 mmol) in DMF (3 mL) at 0° C. was added K2CO3 (203 mg, 1.47 mmol). The completion of the reaction was monitored by TLC (EtOAc:Hex 1:1, Rf=0.90). After the completion of the reaction, 4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidine (340 mg, 1.47 mmol) and K2CO3 (406 mg, 2.94 mmol) were added at 0° C. The reaction was warmed to rt and stirred for 30 min. The reaction was heated to 40° C. and maintained for 1 h. The reaction was cooled to rt, poured in to H2O (50 mL) and extracted with EtOAc (50 mL, two times). The EtOAc was dried over MgSO2 and concentrated under vacuum. The crude product was purified over SiO2 (EtOAc:Hex=1:1, Rf=0.49) to afford Compound B130 (501 mg; 76.7%). 1H-NMR (DMSO-d6): 9.60 (1H, s), 8.28 (1H, s), 7.45˜7.29 (3H, m), 4.64 (2H, m), 3.59˜3.52 (4H, m), 3.41˜3.49 (2H, m), 2.29˜2.25 (2H, b), 1.96˜1.86 (2H, m), 1.39 (6H, d) ppm. LCMS: 426.43.

1. additionwere added at 0° C
2. temperatureThe reaction was heated to 40° C.
3. temperaturemaintained for 1 h
4. temperatureThe reaction was cooled to rt
5. extractionextracted with EtOAc (50 mL, two times)
6. dry with materialThe EtOAc was dried over MgSO2
7. concentrationconcentrated under vacuum
8. customThe crude product was purified over SiO2 (EtOAc:Hex=1:1, Rf=0.49)
9. customto afford Compound B130 (501 mg; 76.7%)