Trifluoroacetic acid → HCID 89761619, compound

Participants

Reaction Steps

To a solution of tert-butyl 4-(5-amino-2-(7-(N-(4-methoxybenzyl)-N-(thiazol-2-yl)sulfamoyl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (0.105 g, 0.152 mmol) in dry acetonitrile (1.522 mL) at 0° C. was added tert-butyl nitrite (0.026 mL, 0.213 mmol) followed by dropwise addition of azidotrimethylsilane (0.024 mL, 0.183 mmol). The resulting mixture was stirred for 20 minutes, at which time no conversion to the desired was observed. Additional tert-butyl nitrite (0.052 mL) and azidotrimethylsilane (0.048 mL) were added at 0° C. and the reaction was once again stirred at RT for 1 h. Conversion was observed, but starting material was still the major reaction component, so the reaction was recooled to 0° C. and 0.156 mL of t-Bu nitrite was added, followed by dropwise addition of 0.144 mL of TMS-azide. After 20 minutes at RT, the reaction was complete and was concentrated under a vacuum. DCM (1.0 mL) was added, followed by TFA (0.235 mL, 3.04 mmol), and the reaction was stirred at RT for 1 h. The material was concentrated under a vacuum and purified by reverse-phase preparative HPLC using a Phenomenex Luna column, 5 micron, C18(2), 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 25% to 90% over 20 min to provide 4-(4-azido-2-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide bis(2,2,2-trifluoroacetate) (0.028 g, 0.039 mmol) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.30-2.44 (m, 2 H) 3.19 (m, J=5.20 Hz, 2 H) 3.47-3.56 (m, 2 H) 3.62-3.70 (m, 2 H) 4.29 (t, J=4.25 Hz, 2 H) 5.76-5.83 (m, 1 H) 6.29 (d, J=8.31 Hz, 1 H) 6.79 (d, J=4.50 Hz, 1 H) 7.02 (d, J=2.74 Hz, 1 H) 7.08-7.15 (m, 2 H) 7.17 (dd, J=8.56, 2.69 Hz, 1 H) 7.22 (d, J=4.60 Hz, 1 H) 7.38 (d, J=8.51 Hz, 1 H) 8.76 (br. s., 2 H) 12.53 (br. s., 1H); m/z (ESI) 496.0 (M+H)+.

Provenance & Evidence