6-BROMO-3,4-DIHYDRO-2H-PYRIDO[3,2-B][1,4]OXAZINE

Step 4 To a solution of Compound (9) (3.12 g, 13.7 mmol) in tetrahydrofuran (50 mL), borane-tetrahydrofuran complex (33 mL, 33.0 mmol) was added at room temperature. The solution was then stirred at 90°C for 1.5 hours. Methanol (2.0 mL) was added to the reaction solution, and then the mixture was stirred at 90°C for 20 minutes. The reaction solution was concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with aqueous saturated sodium bicarbonate, dried with anhydrous magnesium sulfate, and then concentrated in vacuo to yield subject compound (10) (3.17 g, 100percent) as a yellow powder.Under ice bath conditions, Borane in tetrahydrofuran (5.5 mL, 5.5 mmol, 1.0 M) Add dropwise to compound 3.2 (500 mg, 2.19 mmol) In a solution of tetrahydrofuran (25 mL), The reaction system was stirred under reflux with heating for 1 hour. The reaction was then carefully quenched with methanol (10 drops) under reflux. The mixture was cooled to room temperature and concentrated under reduced pressure to remove solvent. The residue was chromatographed on silica gel ( petroleum ether / ethyl acetate = 5/1) Purification afforded compound 23.1 (470 mg, yield: 99percent) It is a white solid.Part IV- Synthesis of 6-Bromo-3, 4-dihydro-2H-pyrido[3, 2-b] [1, 4]oxazine; 6-Bromo-4H-pyrido[3, 2-b][1, 4]oxazin-3-one (1.35 g, 5.89 mmol) was dissolved inTHF (40 mL). Boranedimethylsulphide complex (2.0 Min THF, 5.89 mL, 11.79 mmol) wasadded and the resulting mixture heated to 70 °C under nitrogen for 15 minutes. Next, thereaction mixture was cooled to room temperature, quenched with methanol ( ~5 mL ), and then dried under vacuum to obtain a white solid. The crude material was dissolved indichloromethane and washed with H20. The aqueous phase was discarded and the organicphase was dried under vacuum to give 6-bromo-3, 4-dihydro-2H-pyrido[3, 2-b ][1, 4]oxazine.Yield: 1.1 g (87percent). LCMS (ESI): calc. C7H7BrN20 = 214, 216; obs. M+H = 215, 217.To a solution of 6-bromo-3-(2-bromoethoxy)-2-nitropyridine (4.5 g, 13.8 mmol) in glacial acetic acid (23 ml) was added iron (powder, 3.08 g, 55.2 mmol) in one portion. The reaction mixture was heated to 90°C during 5 hours, then cooled down, diluted in ethyl acetate and filtered through a silica gel plug using ethyl acetate as eluent. After evaporation, the residue was dissolved in DMF (50 ml). Potassium carbonate (5.72 g, 41.4 mmol) was added and the mixture was heated to 90°C for 2 hours, then to 70°C overnight. After evaporation of solvent, the residue was dissolved in DCM, salts were removed by filtration, and the crude compound was purified by silica gel flash chromatography (30 to 50percent ethyl acetate in petroleum ether) to give 6-bromo-3, 4-dihydro-2H-pyrido[3, 2- b][l, 4]oxazine as a pale yellow oil (1.64 g, 55percent); Mass Spectrum [M+H]

Molecular Weight:215.05
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:213.97418
Monoisotopic Mass:213.97418
Topological Polar Surface Area:34.2
Heavy Atom Count:11
Complexity:144
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes