7-Bromo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine

To a solution of 3, 4-dihydro-2H-pyrido [3, 2-b] [1, 4] oxazine (500 mg, 3.67 mmol) in DMF (10 mL) was added NBS (719 mg, 4.04 mmol) at 0°C. The mixture was stirred at 0°C for 2 h. The mixture was quenched with sat. NaHCO(Example 5 Synthesis of Compounds I-114, I-110, and I-111) [Show Image][Show Image]Step 1 To a solution of Compound (14) (4.00 g, 29.4 mmol) in dimethylformamide (40 mL), N-bromosuccinimide (6.27 g, 35.3 mmol) was added. The solution was then stirred at room temperature for 1 hour. Aqueous saturated sodium bicarbonate (100 mL) and water (100 mL) were then thereto. The precipitated powder was filtered, and then washed with water. The filtrate was then extracted with diisopropyl ether. The organic layer was washed sequentially with water and saturated brine, then dried with anhydrous magnesium sulfate, and concentrated in vacuo to yield subject compound (15) (1.79 g, 28percent) as a pale yellow powder.To a solution of 3, 4-dihydro-2H-pyrido [3, 2-b] [1, 4] oxazine (500 mg, 3.67 mmol) in DMF (10 mL) was added NBS (719 mg, 4.04 mmol) at 0C. The mixture was stirred at 0C for 2 h. The mixture was quenched with sat. NaHCO3 aq. ' and water at 0C and stirred at 0C for 20 min. The precipitate was collected by filtration. The solid was washed with water and dried in vacuo to give the title compound (549 mg, 2.55 mmol, 69.5%) as brown solids. . . (3284) MS (ESI+), found 215.2 (M+H) (3285) 1H NMR (300 MHz, CDC13) 5:3.50-3.58 (2H, m) , 4.18-4.26 (2H, m) , 4.82 (1H, brs), 7.10 (1H, d, J = 1.9 Hz), 7.72 (1H, d, J = 2.3 Hz)(Example 5 Synthesis of Compounds I-114, I-110, and I-111) [Show Image][Show Image]Step 1 To a solution of Compound (14) (4.00 g, 29.4 mmol) in dimethylformamide (40 mL), N-bromosuccinimide (6.27 g, 35.3 mmol) was added. The solution was then stirred at room temperature for 1 hour. Aqueous saturated sodium bicarbonate (100 mL) and water (100 mL) were then thereto. The precipitated powder was filtered, and then washed with water. The filtrate was then extracted with diisopropyl ether. The organic layer was washed sequentially with water and saturated brine, then dried with anhydrous magnesium sulfate, and concentrated in vacuo to yield subject compound (15) (1.79 g, 28%) as a pale yellow powder.1H-NMR (DMSO-d6) delta7.62 (1H, d, J= 2.1Hz), 7.14 (1H, d, J =2.1Hz), 6.98 (1H, br s), 4.11 (2H, t, J=4.5Hz), 3.36-3.40 (2H, m) LC/MS (Method A): 0.98 min, [M+H]+= 217.0.AcOH (18 mL) in Fig. 3, 4-dihydro-2H-pyrido[3, 2-b][1, 4]oxazine (1.00 g, 7.35 mmol) to a stirring solution of Br2 (0.472 mL, 9.19 mmol) was added dropwise at 0 C. After stirring the mixture resulting as a result from 0 C for 3 hours, it was warmed to ambient temperature such that the mixture. After the precipitate was filtered, diluted with EtOAc (200 mL) and dried in a high vacuum state was produced F1.Preparation of 7-bromo-4-methyl-3, 4-dihydro-2H-pyrido[3, 2-b][1, 4]oxazine (G2.D) To a solution of To a microwave vial is added R-8 (100 mg, 0.47 mmol), R-9 (44 mg, 0.047 mmol), HP(t-13u)3----13F4 (27 mg, 0.093 mmol), Mo(CO)5 (123 mg, 0.47 mmol) and piperidine (0.14 mE, 1.4 mmol). Contents are dissolved in dioxane (3 mE) then treated with DI3U (0.14 mE, 0.93 mmol) and DIEA (0.33 mE, 1.86 mmol) and heated at 150 C. in the microwave for 30 mm. The mixture is cooled to ambient temperature then filtered through a pad of Celite, concentrated and purified by RHPEC to give Ex 3 (35 mg, 30%).

Molecular Weight:215.05
XLogP3:1.6
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