2H-oxazine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The oxazine of formula XI (0.1 mmol) was added portionwise to concentrated sulfuric acid (2 ml) at 22° C. The solution obtained was cooled to 0° C. and treated with red fuming nitric acid (0.058 ml) and stirring was continued at 0° C. for 2 hours. For the workup, the reaction mixture was slowly added to crushed ice and the pH was adjusted to 10 using a saturated solution of sodium carbonate. The aqueous layer was extracted with ethyl acetate, the organic layer was dried over sodium sulphate and evaporated to afford the pure nitro-oxazine of formula XII. Alternatively, the crude product was purified by flash chromatography on silica-NH2 gel using mixtures of heptane or cyclohexane and ethyl acetate as the eluent to yield the pure nitro-oxazines of formula XII. The solution obtained For the workup, the reaction mixture was slowly added to crushed ice The aqueous layer was extracted with ethyl acetate the organic layer was dried over sodium sulphate evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The oxazine of formula XI (0.1 mmol) was added portionwise to concentrated sulfuric acid (2 ml) at 22° C. The solution obtained was cooled to 0° C. and treated with red fuming nitric acid (0.058 ml) and stirring was continued at 0° C. for 2 hours. For the workup, the reaction mixture was slowly added to crushed ice and the pH was adjusted to 10 using a saturated solution of sodium carbonate. The aqueous layer was extracted with ethyl acetate, the organic layer was dried over sodium sulphate and evaporated to afford the pure nitro-oxazine of formula XII. Alternatively, the crude product was purified by flash chromatography on silica-NH2 gel using mixtures of heptane or cyclohexane and ethyl acetate as the eluent to yield the pure nitro-oxazines of formula XII. The solution obtained For the workup, the reaction mixture was slowly added to crushed ice The aqueous layer was extracted with ethyl acetate the organic layer was dried over sodium sulphate evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 16.6 g (0.597M) of methylthiopseudourea sulfate is added 66 ml of H2O+13.0 g of KOH. With vigorous stirring, 20 g (71.9 mM) of ethyl-m-fluorobenzoylacetate is added and the reaction mixture is allowed to stir, at ambient temperature, for 18 hours. The solids are filtered and washed well with H2O followed by diethylether. The crude title compound is dried at 60° C. in a vacuum over to yield 16.0 g (>100 percent). To 6.8 g of crude powdered oxazine is added 100 ml of H2O and heated to 70° C., cooled, filtered and washed solids. Yield of 2-amino-6-m-fluorophenyl-1,3-oxazine-4-one of 3.60 g (53 percent of rec. yield). The solids are filtered washed well with H2O The crude title compound is dried at 60° C. in a vacuum over to yield 16.0 g (>100 percent) heated to 70° C. cooled filtered washed solids

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxazine XXIV (1.27 mmol) was dissolved in sulfuric acid (10.2 g, 5.57 ml, 102 mmol, Eq: 80). The light yellow solution was cooled in an ethanol/ice bath. Nitric acid fuming (1.78 mmol) was added dropwise over a period of 1 minute. The mixture was stirred under ice-bath cooling for 30 minutes and poured carefully onto ice-water (30 ml). The mixture was basified with a 5N NaOH solution and extracted 3 times with ethyl acetate. The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified on silica gel [Eluent: Heptane/ethyl acetate (0% to 50%)] to afford the pure nitro-oxazine XXV. The light yellow solution was cooled in an ethanol/ice bath cooling for 30 minutes poured carefully onto ice-water (30 ml) extracted 3 times with ethyl acetate The combined extracts were dried over Na2SO4 filtered concentrated in vacuo The crude product was purified on silica gel [Eluent: Heptane/ethyl acetate (0% to 50%)]

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To concentrated sulfuric acid (2 ml) was added portion wise the oxazine XI (0.1 mmol) at 22° C., the solution obtained was cooled to 0° C. and treated with red fuming nitric acid (HNO3) (0.058 ml) and stiffing was continued at 0° C. for 2 h. The reaction mixture was slowly added to crushed ice, the pH was adjusted to 10 using a saturated sodium carbonate solution, the aqueous layer was extracted with AcOEt, the organic layer was dried and evaporated to afford the pure nitro-oxazine XII. the solution obtained The reaction mixture was slowly added to crushed ice the aqueous layer was extracted with AcOEt the organic layer was dried evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetrachloropyrazine (22 g, 0.1 mol), ethylaminoethanol (9 g, 0.1 mol), and crushed KOH (16.5 g, 85% assay, 0.25 mol) were contacted overnight in 200 ml of refluxing benzene. Work-up gave a mixture of the oxazine (25%) and of the O-adduct (75%). The mixture was dissolved in THF and triethylamine (20 g, 0.2 mol) was added and held at reflux temperature for 6 days. The solid was filtered, the THF rotary evaporated, and the residual oil was partitioned between water and CH2Cl2. The organic layer was dried (MgSO4) and rotary evaporated to leave an oily residue. This was recrystallized from hexane and IPA to give two crops totaling 2.8 g (12% yield), m.p. 108°-10°. Work-up gave at reflux temperature for 6 days The solid was filtered the THF rotary evaporated, and the residual oil was partitioned between water and CH2Cl2 The organic layer was dried (MgSO4) rotary evaporated to leave an oily residue This was recrystallized from hexane and IPA to give two crops

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetrachloropyrazine (22 g, 0.1 mol), ethylaminoethanol (9 g, 0.1 mol), and crushed KOH (16.5 g, 85% assay, 0.25 mol) were contacted overnight in 200 ml of refluxing benzene. Work-up gave a mixture of the oxazine (25%) and of the O-adduct (75%). The mixture was dissolved in THF and triethylamine (20 g, 0.2 mol) was added and held at reflux temperature for 6 days. The solid was filtered, the THF rotary evaporated, and the residual oil was partitioned between water and CH2Cl2. The organic layer was dried (MgSO4) and rotary evaporated to leave an oily residue. This was recrystallized from hexane and IPA to give two crops totaling 2.8 g (12% yield), m.p. 108°-10°. Work-up gave at reflux temperature for 6 days The solid was filtered the THF rotary evaporated, and the residual oil was partitioned between water and CH2Cl2 The organic layer was dried (MgSO4) rotary evaporated to leave an oily residue This was recrystallized from hexane and IPA to give two crops

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 16.6 g (0.597 M) of methylthiopseudourea sulfate is added 66 ml of H2O+13.0 g of KOH. With vigorous stirring, 20 g (71.9 mM) of ethyl-m-fluorobenzoylacetate is added and the reaction is allowed to stir, at ambient temperature, for 18 hours. The solids are filtered and washed well with H2O followed by diethylether. The crude title compound is dried at 60° C. in a vacuum over to yield 16.0 g (>100 percent). To 6.8 g of crude powdered oxazine is added 100 ml of H2O and heated to 70° C., cooled, filtered and washed solids. Yield of 2-amino-6-m-fluorophenyl-1,3-oxazine-4-one of 3.60 g (53 percent of rec. yield). The solids are filtered washed well with H2O The crude title compound is dried at 60° C. in a vacuum over to yield 16.0 g (>100 percent) heated to 70° C. cooled filtered washed solids