反应详情

温度

-78 °C

n-Butyllithium (2.5 M solution in hexanes, 74 μL, 0.185 mmol) was slowly added drop-wise to a −78° C. solution of 2-(4-iodo-1-methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)pyridine (C14) (50 mg, 0.14 mmol) in tetrahydrofuran (2 mL). The reaction mixture was allowed to stir at −78° C. for 1 hour, and then a solution of 4-(azetidin-1-yl)-6-chloropyrimidine-5-carbaldehyde (C12) (28.1 mg, 0.142 mmol) in tetrahydrofuran (1 mL) was added. Stirring was continued for 1.5 hours at −78° C., then water was added, and the reaction mixture was removed from the cooling bath. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with saturated aqueous sodium chloride solution, dried, filtered, and concentrated in vacuo. Purification using silica gel chromatography (Eluent: 94:5:1 dichloromethane/methanol/triethylamine) provided the product. Yield: 40 mg, 0.094 mmol, 67%. LCMS m/z 425.2, 427.2 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.17-2.26 (m, 2H), 3.72 (s, 3H), 3.89-3.97 (m, 2H), 4.23-4.31 (m, 2H), 6.32 (s, 1H), 7.58 (s, 1H), 7.79 (br d, J=8 Hz, 1H), 7.85 (s, 1H), 7.92 (br dd, J=8, 2 Hz, 1H), 8.58 (br d, J=2 Hz, 1H).

1. customto a −78° C.
2. stirringStirring
3. waitwas continued for 1.5 hours at −78° C.
4. customthe reaction mixture was removed from the cooling bath
5. extractionThe aqueous layer was extracted with ethyl acetate
6. washthe combined organic layers were washed with saturated aqueous sodium chloride solution
7. customdried
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customPurification
11. customprovided the product