4H-1,4-benzothiazin-3-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of (2H)1,4-benzothiazin-3(4H)-one (20.0 g, 121.1 mmol) in anhydrous tetrahydrofuran (100 mL) was added to a stirred suspension of lithium aluminum hydride in anhydrous tetrahydrofuran (80 mL) under nitrogen at 0° C. The mixture was heated at reflux for 2 hrs and then poured into a mixture of ethyl acetate (300 mL) and ice (500 g). The organic layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic layer was dried and concentrated under reduced pressure to provide 17.68 g (96.5%) of the desired compound which was used without further purification. The mixture was heated at reflux for 2 hrs The organic layer was separated the aqueous layer extracted with ethyl acetate The combined organic layer was dried concentrated under reduced pressure

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl 3-[1-[4-(2-bromoethoxy)benzyl]-3-phenyl-1H-pyrazol-4-yl]propionate (883 mg), 2H-1,4-benzothiazin-3(4H)-one (320 mg), potassium carbonate (530 mg) and N,N-dimethylformamide (10 ml) was stirred at 80° C. for 8 hours. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed successively with dilute hydrochloric acid and saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to obtain a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio). After a mixture of the resulting colorless oily substance, 1N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml) and ethanol (5 ml) was stirred at room temperature for 3 hours, 1N hydrochloric acid (5 ml) was added to the mixture, and then the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated to obtain 3-[1-[4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acid (680 mg, yield: 69%) as a colorless amorphous substance. extracted with ethyl acetate The ethyl acetate layer was washed successively with dilute hydrochloric acid and saturated aqueous sodium chloride solution dried (MgSO4) concentrated to obtain a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio) After a mixture of the resulting colorless oily substance, 1N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml) and ethanol (5 ml) was stirred at room temperature for 3 hours 1N hydrochloric acid (5 ml) was added to the mixture the mixture was extracted with ethyl acetate The ethyl acetate layer was washed with a saturated aqueous sodium chloride solution dried (MgSO4) concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of (2H)1,4-benzothiazin-3(4H)-one (20.0 g, 121.1 mmol) in anhydrous tetrahydrofuran (100 mL) was added to a stirred suspension of lithium aluminum hydride in anhydrous tetrahydrofuran (80 mL) under nitrogen at 0° C. The mixture was heated at reflux for 2 hrs and then poured into a mixture of ethyl acetate (300 mL) and ice (500 g). The organic layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic layer was dried and concentrated under reduced pressure to provide 17.68 g (96.5%) of the desired compound which was used without further purification. The mixture was heated at reflux for 2 hrs The organic layer was separated the aqueous layer extracted with ethyl acetate The combined organic layer was dried concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of (2H)1,4-benzothiazin-3(4H)-one (20.0 g, 121.1 mmol) in anhydrous tetrahydrofuran (100 mL) was added to a stirred suspension of lithium aluminum hydride in anhydrous tetrahydrofuran (80 mL) under nitrogen at 0° C. The mixture was heated at reflux for 2 hrs and then poured into a mixture of ethyl acetate (300 mL) and ice (500 g). The organic layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic layer was dried and concentrated under reduced pressure to provide 17.68 g (96.5%) of the desired compound which was used without further purification. The mixture was heated at reflux for 2 hrs The organic layer was separated the aqueous layer extracted with ethyl acetate The combined organic layer was dried concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2H-1,4-benzothiazine-3(4H)-one (1.0 g, 6.05 mmol) and Cs2CO3 (2.96 g, 9.08 mmol) were dissolved in dry acetonitrile (20 mL) under nitrogen atmosphere and stirred at rt for 30 min. 3-chloro-1-iodopropane (1.37 g, 6.66 mmol) dissolved in acetonitrile (4 mL) was added via a syringe. The reaction mixture was stirred at rt for 18 hours and concentrated in vacuo. Water (150 mL) was added and the reaction mixture was extracted with ethyl acetate (3×150 mL). The combined organic phases were dried (MgSO4) and concentrated in vacou to give 1.45 g of crude. The crude product was subjected to CC[eluent:Heptane:EtOAC(4:1)] to give the pure title compound as a slightly yellow oil. Yield 1.37 g, 90.2%. Rf=0.24 [Heptane:EtOAC(4:1)], 1H NMR (CDCl3): δ 2.14 (m, 2H), 3.38 (s, 2H), 3.36 (t, 2H), 4.17 (t, 2H), 7.03 (t, 1H), 7.18 (d, 1H), 7.26 (t, 1H), 7.37 (d, 1H). 13C NMR (CDCl3): δ 30.61, 31.81, 42.48, 42.66, 117.87, 123.78, 124.29, 127.52, 127.52, 128.78, 139.40, 165.51 was added via a syringe The reaction mixture was stirred at rt for 18 hours concentrated in vacuo Water (150 mL) was added the reaction mixture was extracted with ethyl acetate (3×150 mL) The combined organic phases were dried (MgSO4) concentrated in vacou to give 1.45 g of crude