ethanamine;hydrochloride

Conditions: temp:100.01; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:

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

Procedure: To a stirred solution of 2-chloro-1-(6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethanone (855 mg, 3.14 mmol) in dioxane (15 mL) and triethylamine (0.881 mL, 6.27 mmol) was added ethanamine hydrochloride (1.278 g, 15.68 mmol) as a solution in water (7.50 mL). The resulting mixture was stirred vigorously at room temperature over the weekend. The mixture was then diluted with water and extracted with dichloromethane (2×). The combined organics were dried, filtered, concentrated, and then chromatographed in 1:9 (2M NH3 in methanol):ethyl acetate, giving the desired product (775 mg, 88%). 1H NMR (DMSO-d6) δ 8.37 (d, J=2.4 Hz, 1H), 7.93 (dd, J=8.7, 2.4 Hz, 1H), 7.50 (d, J=8.7 Hz, 1H), 3.97-3.90 (m, 2H), 3.52 (s, 2H), 3.37-3.33 (m, 2H), 2.58-2.50 (m, 2H), 2.07 (brs, 1H), 1.00 (t, J=7.0 Hz, 3H); ESI-MS (m/z, %): 282 (MH+, 100). extracted with dichloromethane (2×) The combined organics were dried filtered concentrated chromatographed in 1:9 (2M NH3 in methanol)

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

Procedure: A solution of 2-chloro-1-(7-nitro-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethanone (9.9 g, 38.6 mmol) in anhydrous acetonitrile (250 mL) under positive argon pressure was treated with K2CO3 (42.7 g, 309 mmol) to give a yellow suspension. The mixture was cooled to 0° C. and treated with ethanamine hydrochloride (15.7 g, 193 mmol). The reaction was brought to room temperature and stirred for 2.5 hours. The mixture was then filtered through a pad of Celite, washed with CH2Cl2 (500 mL), and concentrated. The residue was subjected to flash chromatography on silica gel using EtOAc, followed by 2.5:97.5 (2M NH3 in MeOH):CH2Cl2 to give a yellow solid (7.73 g, 76%). 1H-NMR (DMSO-d6) δ 8.29 (d, J=9.0 Hz, 1H), 7.80 (dd, J=2.7, 9.3 Hz, 1H), 7.71 (d, J=2.7 Hz, 1H), 4.36 (t, J=4.2 Hz, 2H), 3.93 (t, J=4.8 Hz, 2H), 3.71 (s, 2H), 2.62 (q, J=7.2 Hz, 2H), 1.05 (t, J=7.2 Hz, 3H). ESI-MS (m/z, %): 266.1 (MH+, 100). to give a yellow suspension was brought to room temperature The mixture was then filtered through a pad of Celite washed with CH2Cl2 (500 mL) concentrated

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

Procedure: 4-Ethylamino-3-nitro-benzoic acid methyl ester (8.3 g) was prepared by following General Procedure A starting from methyl 4-chloro-3-nitrobenzoate (10.0 g), DIEA (1.6 mL) and ethylamine hydrochloride salt (4.5 g) in DMF (50.0 mL). The crude product was used in the next step without further purification. The crude product was used in the next step without further purification

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

Procedure: 4-Ethylamino-3-nitro-benzoic acid methyl ester (8.3 g) was prepared by following General Procedure A starting from methyl 4-chloro-3-nitrobenzoate (10.0 g), DIEA (1.6 mL) and ethylamine hydrochloride salt (4.5 g) in DMF (50.0 mL). The crude product was used in the next step without further purification. The crude product was used in the next step without further purification

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

Procedure: 16.6 g (130 mmol) oxalyl chloride are added to 15.0 g (65 mmol) 2-(4-bromo-phenyl)-propionic acid (Bioorg. Med. Chem. Lett. 2010, 20, 887) in 75 mL DCM at 0° C. The cooling is removed and the mixture is stirred for 2 h under reflux. After that time, the solvent is evaporated and the residue is taken up in 70 mL THF. 3.20 g (39 mmol) ethylamine hydrochloride and 66.0 g (655 mmol) TEA are added and the mixture is stirred for 16 h at rt. After that time, iced water is added, the mixture is extracted with EtOAc and the organic layer is dried over sodium sulphate. The solvent is evaporated and the residue is purified by column chromatography (silica gel). The cooling is removed under reflux After that time, the solvent is evaporated the mixture is stirred for 16 h at rt the mixture is extracted with EtOAc the organic layer is dried over sodium sulphate The solvent is evaporated the residue is purified by column chromatography (silica gel)