1-bromo-2-(2-methoxyethoxy)benzene

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-bromo-2-(2-methoxyethoxyl)benzene (302.0 mg, 1.31 mmol), INTERMEDIate M (500 mg, 1.19 mmol), Pd2(dba)3 (76.0 mg, 0.0837 mmol), Xantphos (69.0 mg, 0.119 mmol) and sodium-tert-butoxide (229.0 mg, 2.39 mmol) in toluene (10 mL) was degassed with nitrogen for 10 minutes. The reaction mixture was subjected for heating at 100° C. for 1 h under microwave. After completion, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×15 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the crude material which was purified by combiflash column chromatography (column size: 12 g; elution: 12% ethyl acetate in hexane) to get N-(4-methoxybenzyl)-4-(2-(2-methoxyethoxyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (300 mg, 44.2%) as yellow solid. MS (ESI, positive ion) m/z: 568.03 (M+1). was degassed with nitrogen for 10 minutes After completion, the reaction mixture was diluted with water (10 mL) extracted with ethyl acetate (3×15 mL) The organic layer was dried over sodium sulfate concentrated under reduced pressure to obtain the crude material which was purified by combiflash column chromatography (column size: 12 g; elution: 12% ethyl acetate in hexane)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromophenol (500.0 mg, 2.89 mmol) in DMF (5 mL) was added cesium carbonate (2.82 g, 8.67 mmol). To this mixture was added 1-chloro-2-methoxyethane (0.26 mL, 2.89 mmol, Aldrich) and the mixture was heated at 90° C. for 4 h. After completion, the reaction mixture was diluted with water (3 mL) and extracted with ethyl acetate (2×10 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to get 1-bromo-2-(2-methoxyethoxyl)benzene (400 mg, 60.2%) as clear liquid that was used as such for next step without any purification. 1H NMR (400 MHz, DMSO) δ 7.57 (dd, J=7.9, 1.5 Hz, 1H), 7.39-7.24 (m, 1H), 7.13-7.05 (m, 1H), 6.89 (td, J=7.7, 1.2 Hz, 1H), 4.17 (t, J=4.6 Hz, 2H), 3.69 (t, J=4.6 Hz, 2H), 3.33 (s, 3H). MS (ESI, positive ion) m/z: 231.08 (M+1). extracted with ethyl acetate (2×10 mL) The organic layer was dried over sodium sulfate concentrated under reduced pressure

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromophenol (500.0 mg, 2.89 mmol) in DMF (5 mL) was added cesium carbonate (2.82 g, 8.67 mmol). To this mixture was added 1-chloro-2-methoxyethane (0.26 mL, 2.89 mmol, Aldrich) and the mixture was heated at 90° C. for 4 h. After completion, the reaction mixture was diluted with water (3 mL) and extracted with ethyl acetate (2×10 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to get 1-bromo-2-(2-methoxyethoxyl)benzene (400 mg, 60.2%) as clear liquid that was used as such for next step without any purification. 1H NMR (400 MHz, DMSO) δ 7.57 (dd, J=7.9, 1.5 Hz, 1H), 7.39-7.24 (m, 1H), 7.13-7.05 (m, 1H), 6.89 (td, J=7.7, 1.2 Hz, 1H), 4.17 (t, J=4.6 Hz, 2H), 3.69 (t, J=4.6 Hz, 2H), 3.33 (s, 3H). MS (ESI, positive ion) m/z: 231.08 (M+1). extracted with ethyl acetate (2×10 mL) The organic layer was dried over sodium sulfate concentrated under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-bromo-2-(2-methoxyethoxyl)benzene (302.0 mg, 1.31 mmol), INTERMEDIate M (500 mg, 1.19 mmol), Pd2(dba)3 (76.0 mg, 0.0837 mmol), Xantphos (69.0 mg, 0.119 mmol) and sodium-tert-butoxide (229.0 mg, 2.39 mmol) in toluene (10 mL) was degassed with nitrogen for 10 minutes. The reaction mixture was subjected for heating at 100° C. for 1 h under microwave. After completion, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×15 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the crude material which was purified by combiflash column chromatography (column size: 12 g; elution: 12% ethyl acetate in hexane) to get N-(4-methoxybenzyl)-4-(2-(2-methoxyethoxyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (300 mg, 44.2%) as yellow solid. MS (ESI, positive ion) m/z: 568.03 (M+1). was degassed with nitrogen for 10 minutes After completion, the reaction mixture was diluted with water (10 mL) extracted with ethyl acetate (3×15 mL) The organic layer was dried over sodium sulfate concentrated under reduced pressure to obtain the crude material which was purified by combiflash column chromatography (column size: 12 g; elution: 12% ethyl acetate in hexane)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromophenol (500.0 mg, 2.89 mmol) in DMF (5 mL) was added cesium carbonate (2.82 g, 8.67 mmol). To this mixture was added 1-chloro-2-methoxyethane (0.26 mL, 2.89 mmol, Aldrich) and the mixture was heated at 90° C. for 4 h. After completion, the reaction mixture was diluted with water (3 mL) and extracted with ethyl acetate (2×10 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to get 1-bromo-2-(2-methoxyethoxyl)benzene (400 mg, 60.2%) as clear liquid that was used as such for next step without any purification. 1H NMR (400 MHz, DMSO) δ 7.57 (dd, J=7.9, 1.5 Hz, 1H), 7.39-7.24 (m, 1H), 7.13-7.05 (m, 1H), 6.89 (td, J=7.7, 1.2 Hz, 1H), 4.17 (t, J=4.6 Hz, 2H), 3.69 (t, J=4.6 Hz, 2H), 3.33 (s, 3H). MS (ESI, positive ion) m/z: 231.08 (M+1). extracted with ethyl acetate (2×10 mL) The organic layer was dried over sodium sulfate concentrated under reduced pressure