7-Chloro-2H-1,4-benzoxazin

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: Using 7-chloro-4H-benzo[1,4]oxazin-3-one (2.3 g, 13.5 mmol) and borane-THF (40 mL of a 1M solution in THF, 40 mmol) in THF (40 mL) to yield the title compound as a cream solid (2.2 g, 96%). δH (CDCl3) 3.34-3.40 (2H, m), 4.16-4.28 (2H, m), 6.51-6.55 (1H, m), 6.59 (1H, d, J 2.4 Hz), 6.68 (1H, dd, J 8.1, 0.4 Hz). LCMS (ES+) 170 (M+H)+.

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: 7-Chloro-4H-benzo[1,4]oxazin-3-one (81MF2271a) (1.74 g, 9.47 mmol), Cs2CO3 (4.63 g, 14.2 mmol) and 3-chloro-1-iodopropane (2.13 g, 10.4 mmol) were mixed according to GP6. CC (SiO2; Heptane/EtOAc 10:1-5) gave the title compound (81MF2271b) (1.95 g, 79%). 1H NMR (CDCl3) δ 7.03-6.96 (m, 3H), 4.59 (s, 2H), 4.07 (t, J=7.2 Hz, 2H), 3.61 (t, J=6.4 Hz, 2H), 2.17-2.10 (m, 2H); 13C NMR (CDCl3) δ 164.0, 146.0, 129.1, 127.3, 123.0, 117.8, 115.5, 67.7, 42.4, 39.2, 30.0.

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

実験手順: Using 7-chloro-4H-benzo[1,4]oxazin-3-one (2.3 g, 13.5 mmol) and borane-THF (40 mL of a 1M solution in THF, 40 mmol) in THF (40 mL) to yield the title compound as a cream solid (2.2 g, 96%). δH (CDCl3) 3.34-3.40 (2H, m), 4.16-4.28 (2H, m), 6.51-6.55 (1H, m), 6.59 (1H, d, J 2.4 Hz), 6.68 (1H, dd, J 8.1, 0.4 Hz). LCMS (ES+) 170 (M+H)+.

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

実験手順: 7-Chloro-4H-benzo[1,4]oxazin-3-one (81MF2271a) (1.74 g, 9.47 mmol), Cs2CO3 (4.63 g, 14.2 mmol) and 3-chloro-1-iodopropane (2.13 g, 10.4 mmol) were mixed according to GP6. CC (SiO2; Heptane/EtOAc 10:1-5) gave the title compound (81MF2271b) (1.95 g, 79%). 1H NMR (CDCl3) δ 7.03-6.96 (m, 3H), 4.59 (s, 2H), 4.07 (t, J=7.2 Hz, 2H), 3.61 (t, J=6.4 Hz, 2H), 2.17-2.10 (m, 2H); 13C NMR (CDCl3) δ 164.0, 146.0, 129.1, 127.3, 123.0, 117.8, 115.5, 67.7, 42.4, 39.2, 30.0.

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

実験手順: 7-Chloro-4H-benzo[1,4]oxazin-3-one (81MF2271a) (1.74 g, 9.47 mmol), Cs2CO3 (4.63 g, 14.2 mmol) and 3-chloro-1-iodopropane (2.13 g, 10.4 mmol) were mixed according to GP6. CC (SiO2; Heptane/EtOAc 10:1-5) gave the title compound (81MF2271b) (1.95 g, 79%). 1H NMR (CDCl3) d 7.03-6.96 (m, 3H), 4.59 (s, 2H), 4.07 (t, J=7.2 Hz, 2H), 3.61 (t, J=6.4 Hz, 2H), 2.17-2.10 (m, 2H); 13C NMR (CDCl3) d 164.0, 146.0, 129.1, 127.3, 123.0, 117.8, 115.5, 67.7, 42.4, 39.2, 30.0.

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

実験手順: 7-Chloro-4H-benzo[1,4]oxazin-3-one (81MF2271a) (1.74 g, 9.47 mmol), Cs2CO3 (4.63 g, 14.2 mmol) and 3-chloro-1-iodopropane (2.13 g, 10.4 mmol) were mixed according to GP6. CC (SiO2; Heptane/EtOAc 10:1-5) gave the title compound (81MF2271b) (1.95 g, 79%). 1H NMR (CDCl3) δ 7.03-6.96 (m, 3H), 4.59 (s, 2H), 4.07 (t, J=7.2 Hz, 2H), 3.61 (t, J=6.4 Hz, 2H), 2.17-2.10 (m, 2H); 13C NMR (CDCl3) δ 164.0, 146.0, 129.1, 127.3, 123.0, 117.8, 115.5, 67.7, 42.4, 39.2, 30.0.

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

実験手順: 7-Chloro-4H-benzo[1,4]oxazin-3-one (81MF2271a) (1.74 g, 9.47 mmol), Cs2CO3 (4.63 g, 14.2 mmol) and 3-chloro-1-iodopropane (2.13 g, 10.4 mmol) were mixed according to GP6. CC (SiO2; Heptane/EtOAc 10:1-5) gave the title compound (81MF2271b) (1.95 g, 79%). 1H NMR (CDCl3) δ 7.03-6.96 (m, 3H), 4.59 (s, 2H), 4.07 (t, J=7.2 Hz, 2H), 3.61 (t, J=6.4 Hz, 2H), 2.17-2.10 (m, 2H); 13C NMR (CDCl3) δ 164.0, 146.0, 129.1, 127.3, 123.0, 117.8, 115.5, 67.7, 42.4, 39.2, 30.0.

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

実験手順: A mixture of 2-chloro-1-[4-(4-chloro-3-methoxy-phenyl)-piperazin-1-yl]-ethanone (1) (331 mg, 1.1 mmol, 1 equiv) in 5 ml of DMF, 4H-Benzo[1,4]oxazin-3-one (28) (200 mg, 1.1 mmol, 1.0 equiv) and cesium carbonate (710 mg, 2.2 mmol, 2 equiv) was stirred at RT overnight. The reaction solution was diluted with EtOAc, and the organic solution was washed with water. Purification of the crude reaction mixture using flash chromatography provided 7-chloro-4-{2-[4-(4-chloro-3-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-4H-benzo[1,4]oxazin-3-one (29): LCMS Retention time, 2.58 min.; LCMS observed (M+H)+: 450. the organic solution was washed with water Purification of the crude reaction mixture

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

実験手順: A mixture of 2-amino-5-chloro-phenol (27) (2.0 g, 14 mmol, 1 equiv) in 30 ml of THF, chloroacetyl chloride (1.26 ml, 16.8 mmol, 1.2 equiv), and saturated aqueous NaHCO3 50 mL was stirred at RT for 2 hrs and then heated at 80° C. overnight. The reaction mixture was diluted with EtOAc, and washed with water. Purification of the crude product by flash chromatography provided 7-chloro-4H-benzo[1,4]oxazin-3-one (28): LCMS Retention time: 1.48 min.; LCMS observed (M+H)+: 184. heated at 80° C. overnight washed with water Purification of the crude product by flash chromatography