反应详情

To a stirred solution of N′-(3-chloro-6-fluoro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-(1,4-dioxan-2-ylmethyl)-N-methylsulfamide (127 mg, 0.271 mmol) in DMF (7 mL) were added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (113 mg, 0.543 mmol), tri-t-butylphosphonium tetraflroroborate (16 mg, 0.054 mmol), potassium fluoride (52 mg, 0.896 mmol), and Pd2(dba)3 (25 mg, 0.027 mmol). The reaction mixture was purged with N2 for 5 min, heated to 130 C for 9 h, cooled to room temperature, treated with water, and extracted with CH2Cl2 (×3). The combined organics were dried (Na2SO4), concentrated, and purified by prep-HPLC to afford the title compound. 1H NMR (600 MHz, CDCl3) δ 8.99 (d, 1H); 8.31 (d, 1H); 7.91 (s, 1H); 7.90 (m, 2H); 7.81 (s, 1H); 7.36 (d, 1H); 7.26 (d, 1H); 7.17 (d, 1H); 4.00 (s, 3H); 3.64-4.00 (series of m, 7H); 3.36 (dd, 1H); 3.09 (dd, 1H); 2.99 (s, 3H). LRMS (ESI) calc'd for (C24H24F5O5S) [M+H]+, 514.1; found 514.1.

1. customThe reaction mixture was purged with N2 for 5 min
2. temperatureheated to 130 C for 9 h
3. additiontreated with water
4. extractionextracted with CH2Cl2 (×3)
5. dry with materialThe combined organics were dried (Na2SO4)
6. concentrationconcentrated
7. custompurified by prep-HPLC