Borane;tetrahydrofuran → 6-Nitro-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazine

Temperature

55 °C

To a stirred solution of 1-(6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)-2-(pyrrolidin-1-yl)ethanone (750 mg, 2.440 mmol) in tetrahydrofuran (5 mL) was added borane-tetrahydrofuran complex (1M in tetrahydrofuran; 7.32 mL, 7.32 mmol). The resulting mixture was then stirred at 55° C. overnight. The reaction mixture was then cooled to room temperature and quenched carefully via the slow, dropwise addition of methanol (5 mL). The quenched mixture was then stirred at 55° C. overnight. At this time, the reaction was vented to the atmosphere. The mixture was then concentrated and chromatographed on silica gel, eluting with 1:4:5 (2M NH3 in methanol):ethyl acetate:dichloromethane, giving the desired product (654 mg, 91%) as a red oil. 1H NMR (DMSO-d6) δ 7.46 (d, J=2.4 Hz, 1H), 7.36 (dd, J=8.4, 2.1 Hz, 1H), 7.19 (d, J=8.4 Hz, 1H), 3.69-3.65 (m, 2H), 3.50 (t, J=6.9 Hz, 2H), 3.14-3.10 (m, 2H), 2.63 (t, J=6.9 Hz, 2H), 2.56-2.51 (m, 2H), 1.71-1.66 (m, 4H); ESI-MS (m/z, %): 294 (MH+, 100).

1. temperatureThe reaction mixture was then cooled to room temperature
2. customquenched carefully via the slow,
3. additiondropwise addition of methanol (5 mL)
4. stirringThe quenched mixture was then stirred at 55° C. overnight
5. concentrationThe mixture was then concentrated
6. customchromatographed on silica gel
7. washeluting with 1:4:5 (2M NH3 in methanol)

ORD record

ord-21d30d61905c402680b4019753b49fad

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618286B2