Reaction Steps
In a microwave reaction vial, (4aR,9aR)-2,3,4,4a,5,6,7,8,9,9a-decahydro-[1,4]oxazino[2,3-d]azepine dihydrochloride (509 mg; 2.22 mmol) and 5-chloro-1-methyl-4-nitro-pyrazole (322 mg, 2.00 mmol) were dissolved in acetonitrile (16 mL). DIPEA (3.11 mL, 17.77 mmol) was added and the mixture was irradiated with microwave at 130° C. for 60 min. The reaction mixture was diluted with water, extracted with EA 3×. Combined organic layers were dried over Na2SO4 and concentrated to give trans-7-(2-methyl-4-nitro-pyrazol-3-yl)-3,4,4a,5,6,8,9,9a-octahydro-2H-[1,4]oxazino[2,3-d]azepine. To a solution of this compound in DCM (15 mL) was added di-tert-butyl-dicarbonate (727 mg, 3.33 mmol) and DIPEA (1.16 mL, 6.66 mmol). The mixture was stirred at room temperature for 18 h. The crude reaction mixture was concentrated and the residue was purified via silica gel column chromatography (0-100% EA/heptane) to gave the racemic trans-tert-butyl-7-(2-methyl-4-nitro-pyrazol-3-yl)-2,3,4a,5,6,8,9,9a-octahydro-[1,4]oxazino[2,3-d]azepine-4-carboxylate, which was chirally separated on AD column with 20% methanol w/0.1% NH4OH. The first eluting peak of trans-tert-butyl-7-(2-methyl-4-nitro-pyrazol-3-yl)-2,3,4a,5,6,8,9,9a-octahydro-[1,4]oxazino[2,3-d]azepine-4-carboxylate off the SFC chiral separation was converted to 396 following the procedures of Example 354. 1H NMR (400 MHz, DMSO) δ 8.63 (s, 1H), 7.55 (s, 1H), 7.54-7.43 (m, 3H), 7.26 (t, J=8.7 Hz, 2H), 3.64 (s, 3H), 3.24-3.13 (m, 4H), 3.13-2.95 (m, 3H), 2.65 (d, J=5.6 Hz, 2H), 2.60-2.52 (m, 1H), 1.82-1.68 (m, 3H), 1.64-1.53 (m, 2H). LCMS (ES+) m/z 490 (M+1)
