反应详情

4-(3-Fluoroazetidin-1-yl)-3-iodo-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (C10) (500 mg, 1.50 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (910 mg, 2.63 mmol), tris(dibenzylideneacetone)dipalladium(0) (98%, 56 mg, 0.060 mmol), and tricyclohexylphosphine (96%, 35.1 mg, 0.120 mmol) were combined in 1,4-dioxane (10 mL). An aqueous solution of potassium phosphate (97%, 657 mg, 3.00 mmol) in water (5 mL) was added, and the reaction mixture was subjected to microwave irradiation at 150° C. and 200 W for 90 minutes. The reaction mixture was partitioned between ethyl acetate (20 mL) and aqueous phosphate buffer (20 mL), and the aqueous layer was extracted with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography [Gradient: 35% to 100% (10% methanol in ethyl acetate) in heptane] afforded the product as a glass. Yield: 302.3 mg, 1.05 mmol, 70%. LCMS m/z 288.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 3.83-3.92 (m, 2H), 3.93 (s, 6H), 4.14-4.26 (m, 2H), 5.23-5.43 (m, 1H, JHF=58.0 Hz), 7.63 (d, J=0.6 Hz, 1H), 7.99 (br s, 1H), 8.35 (s, 1H).

1. customirradiation at 150° C.
2. customThe reaction mixture was partitioned between ethyl acetate (20 mL) and aqueous phosphate buffer (20 mL)
3. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL)
4. dry with materialThe combined organic layers were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customPurification via silica gel chromatography [Gradient: 35% to 100% (10% methanol in ethyl acetate) in heptane]