Dimethylformamide → HCID 89761590, compound

Participants

Reaction Steps

A reaction vial was charged with 4-(2-bromo-4-isopropylphenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.175 g, 0.285 mmol), Pd(PPh3)4 (0.049 g, 0.043 mmol), and zinc cyanide (0.050 g, 0.427 mmol), and DMF (1.139 ml) was added. The reaction was sealed and heated to 100° C. overnight until complete conversion to the desired product. The reaction was diluted with ethyl acetate and filtered over a membrane, washing with ethyl acetate. The filtrate was then washed with small amounts of water (×4) to remove residual DMF. The organics were dried over sodium sulfate, filtered and concentrated in vacuo to yield a crude yellow oil. The oil was dissolved in methanol and was loaded onto a 2-g SCX column (product eluted with methanol wash). After concentration, the crude product was diluted with DCM (2.0 mL) and TFA (1.0 mL) was added and the reaction was stirred at RT for 30 minutes until complete deprotection. The reaction was then concentrated in vacuo, and was purified by silica gel chromatography eluting with 0-100% ethyl acetate in heptanes to yield 4-(2-cyano-4-isopropylphenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.055 g, 0.125 mmol, 43.8% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (d, J=6.94 Hz, 6 H) 2.93-3.05 (m, 1 H) 3.72-3.77 (m, 2 H) 4.30-4.36 (m, 2 H) 6.42 (d, J=8.41 Hz, 1 H) 6.79 (d, J=4.60 Hz, 1 H) 7.13-7.17 (m, 1 H) 7.18 (d, J=2.15 Hz, 1 H) 7.22 (d, J=4.60 Hz, 1 H) 7.49 (d, J=8.41 Hz, 1 H) 7.68 (dd, J=8.46, 2.20 Hz, 1 H) 7.83 (d, J=2.15 Hz, 1 H) 12.58 (br. s., 1 H). m/z (ESI) 441.3 (M+H)+.

Provenance & Evidence