反应详情

温度

100 °C

To a solution of 4-{4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB3) (86.3 mg, 0.184 mmol), trifluoromethanesulfonic acid 4-methylisoquinolin-3-yl ester (54.8 mg, 0.188 mmol), and Pd(PPh3)4 (14 mg, 0.012 mmol) in 1,4-dioxane (2.8 mL, 36 mmol) in a sealable microwave tube was added a solution of Cs2CO3 (118 mg, 0.361 mmol) in H2O (0.80 mL, 44 mmol). The tube was sealed, evacuated and refilled with nitrogen (3×), and heated in the microwave reactor to 100° C. for 30 min. The reaction mixture was diluted with DCM, washed with water and brine, and dried over MgSO4. The crude material was chromatographed on silica gel [20 g/70 mL prepacked cartridge, eluting with DCM→1% MeOH in DCM→2% MeOH in DCM→2.5% MeOH in DCM→3% MeOH in DCM→3.5% MeOH in DCM→4% MeOH in DCM]. Fractions containing the title compound were combined and dried in vacuo, giving the title compound as a glassy solid. 1H NMR (400 MHz, CDCl3): δ=9.22 (s, 1H), 8.30 (d, J=2.4 Hz, 1H), 8.08 (dd, J=0.8, 8.6 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.81 (ddd, J=1.2, 6.8, 8.3 Hz, 1H), 7.71 (d, J=0.8 Hz, 1H), 7.68 (ddd, J=0.8, 7.0, 8.0 Hz, 1H), 7.62 (s, 1H), 7.57 (d, J=2.4 Hz, 1H), 4.85 (brs, 2H), 4.42-4.13 (m, 3H), 2.90 (brt, J=11.2 Hz, 2H), 2.62 (s, 3H), 2.15 (brdd, J=2.0, 12.4 Hz, 2H), 1.95 (dq, J=4.0, 12.0 Hz, 2H), 1.48 (s, 9H). MS(ES+): m/z=485.14 (100) [MH+], 429.12 (66) [MH+-isobutene]. HPLC: tR=2.62 min (polar—5 min, ZQ3).

1. customThe tube was sealed
2. customevacuated
3. additionrefilled with nitrogen (3×)
4. additionThe reaction mixture was diluted with DCM
5. washwashed with water and brine
6. dry with materialdried over MgSO4
7. customThe crude material was chromatographed on silica gel [20 g/70 mL prepacked cartridge, eluting with DCM→1% MeOH in DCM→2% MeOH in DCM→2.5% MeOH in DCM→3% MeOH in DCM→3.5% MeOH in DCM→4% MeOH in DCM]
8. additionFractions containing the title compound
9. customdried in vacuo