tert-butyl 2-(6-amino-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl(methyl)carbamate → tert-butyl methyl(2-(6-(thiophene-2-carboximidamido)-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl)carbamate

Participants

Reaction Steps

To a stirred ethanolic solution of tert-butyl 2-(6-amino-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl(methyl)carbamate (0.118 g, 0.384 mmol) under an argon atmosphere was charged methyl thiophene-2-carbimidothioate hydroiodide (0.219 g, 0.768 mmol), and the resulting yellow solution stirred at room temperature. After 44 hours, argon was bubbled through the mixture, which was then concentrated to residue and partitioned between EtOAc (100 mL) and saturated NaHCO3 solution (10 mL). The aqueous layer (pH˜9) was further extracted with EtOAc, and the combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated to yield an orange residue. The residue was purified on silica gel twice, with the first purification using 100% EtOAc as the eluent and the second purification using 5% (2M NH3 in MeOH)/CH2Cl2 to yield the title compound as a yellow solid (80 mg, 50.0%). 1H NMR (DMSO-d6) δ 7.68 (d, 1H, J=2.9 Hz), 7.57 (d, 1H, J=5.0 Hz), 7.10-7.03 (m, 1H), 6.60 (d, 1H, J=8.1 Hz), 6.30 (m, 3H), 6.00 (dd, 1H, J=8.1, 1.6 Hz), 4.18-4.02 (m, 2H), 3.40-3.21 (m, 6H, merged with H2O peak), 2.81 (s, 3H), 1.34, 1.29 (2×s, 9H); ESI-MS (m/z, %): 417 (MH+, 100).

Provenance & Evidence