反应详情

温度

130 °C

A microwave vial was charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE M, 0.125 g, 0.299 mmol), 2-bromo-5-methoxybenzonitrile (ASDI, 0.111 g, 0.524 mmol), Xantphos (0.035 g, 0.060 mmol), Pd2(dba)3 (0.027 g, 0.030 mmol) and sodium tert-butoxide (0.058 g, 0.599 mmol). The mixture was diluted with Toluene (2.00 ml), and purged with nitrogen, and heated at 130° C. in the microwave for 30 minutes. After cooling to RT, trifluoroacetic acid (0.577 ml, 7.48 mmol) was added to the crude reaction mixture, and the reaction was stirred at RT for 2 h ( ), after which the crude reaction was filtered over a plug of Celite (washing with minimal DCM to flush through the product). The reactions were then dried overnight in a hood and purified using reverse phase mass-directed HPLC. The column used was a Waters Xbridge C18 19×100 mm 10 micron column. The mobile phase was run under gradient conditions using Water and CH3CN with 0.1% trifluoroacetic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.57 (br. s., 1 H) 7.55 (d, J=2.86 Hz, 1 H) 7.51 (d, J=8.94 Hz, 1 H) 7.37 (dd, J=8.94, 2.86 Hz, 1 H) 7.21 (d, J=4.47 Hz, 1 H) 7.16 (d, J=1.83 Hz, 1 H) 7.13 (dd, J=8.48, 1.95 Hz, 1 H) 6.78 (d, J=4.47 Hz, 1 H) 6.29 (d, J=8.59 Hz, 1 H) 4.31-4.37 (m, 2 H) 3.84 (s, 3 H) 3.68-3.73 (m, 2 H). m/z (ESI) 428.1 (M+H)+.

1. custompurged with nitrogen
2. temperatureAfter cooling to RT
3. customreaction mixture
4. customreaction
5. filtrationwas filtered over a plug of Celite (
6. washwashing with minimal DCM
7. customto flush through the product)
8. customThe reactions were then dried overnight in a hood
9. custompurified