反应详情

温度

100 °C

A solution of 3-benzothiazol-2-yl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-ylamine (BB8) (30 mg, 0.080 mmol), 3-(4-iodopyrazol-1-yl)-azetidine-1-carboxylic acid tert-butyl ester (59 mg, 0.17 mmol), potassium carbonate (40 mg, 0.20 mmol), and Pd(dppf)Cl2 (3 mg, 0.01 mmol) in 1,4-dioxane (1.5 mL) and H2O (0.5 mL) was left to stir at 100° C. for 30 min in the microwave reactor. The mixture was passed through PL-Thiol MP SPE and the residue was concentrated in vacuo. The resulting oil was partitioned between EtOAc and water (3×). The combined organic extracts were treated with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by prep TLC (EtOAc:hexane (3:2)), giving 3-[4-(6-Amino-5-benzothiazol-2-ylpyridin-3-yl)-pyrazol-1-yl]-azetidine-1-carboxylic acid tert-butyl ester, MS (ES+): m/z=449 [MH+]. This material was left to stir at rt in a (1:1) DCM:TFA mixture for 15 min. The solid that formed was filtered off and dried in vacuo, affording the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ=4.53 (d, J=8.1 Hz, 1H), 4.58 (d, J=7.3 Hz, 4H), 5.49 (quint, J=7.4 Hz, 1H), 7.49-7.56 (m, 1H), 7.60 (dd, J=15.4, 1.3 Hz, 1H), 8.07 (d, J=8.1 Hz, 1H), 8.12 (d, J=7.8 Hz, 1H), 8.16 (s, 1H), 8.21 (s, 1H), 8.33 (d, J=2.3 Hz, 1H), 8.57 (d, J=2.0 Hz, 1H). MS (ES+): m/z=349.16 (100) [MH+]. HPLC: tR=1.99 min (ZQ2, polar—5 min).

1. concentrationthe residue was concentrated in vacuo
2. customThe resulting oil was partitioned between EtOAc and water (3×)
3. additionThe combined organic extracts were treated with brine
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by prep TLC (EtOAc:hexane (3:2))