5-bromo-2-morpholin-4-ylaniline

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

Procedure: Prepared according to Procedure K, Method 1 using 4,8-dichloro-2,3-dimethylquinoline (104 mg, 460 μmol), 5-bromo-2-morpholinobenzenamine (118 mg, 460 μmol) and 4N hydrochloric acid solution in dioxane (0.050 mL, 200 μmol) in MeOH (1.00 mL) to afford a colorless solid upon purification by chromatography on silica gel, eluting with a Et2O gradient in toluene. 1H NMR (400 MHz, chloroform-d) δ ppm 7.69 (1H, dd, J=7.4, 1.2 Hz), 7.55-7.63 (1H, m), 7.23-7.30 (1H, m), 6.92-6.98 (1H, m), 6.85-6.92 (1H, m), 6.83 (1H, s), 6.18 (1H, d, J=2.3 Hz), 3.80-3.91 (4H, m), 2.92-3.08 (4H, m), 2.71-2.78 (3H, m), 2.23 (3H, s). Prepared to afford a colorless solid upon purification by chromatography on silica gel eluting with a Et2O gradient in toluene

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

Procedure: Prepared according to Procedure K, Method 2 using 4-chloro-2-(2-fluorophenyl)-3-methylquinoline (230 mg, 848 μmol), 5-bromo-2-morpholinobenzenamine (109 mg, 424 μmol) and 4N hydrochloric acid solution in dioxane (0.011 mL, 42 μmol) in NMP (0.50 mL) to afford a colorless solid upon purification by chromatography on silica gel, eluting with EtOAc gradient in hexane. Mass Spectrum (ESI) m/e=492.1 & 494.1 (M+1). Prepared to afford a colorless solid upon purification by chromatography on silica gel eluting with EtOAc gradient in hexane

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

Procedure: Prepared according to Procedure K, Method 1 using 4-chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (131 mg, 480 μmol), 5-bromo-2-morpholinobenzenamine (124 mg, 480 μmol) and 4.0N hydrochloric acid (0.12 mL, 480 μmol) solution in dioxane in MeOH (1.50 mL) to afford a yellow solid after purification by chromatography on silica gel, eluting with EtOAc-hexane solvent mixture. Mass Spectrum (ESI) m/e=493.0 & 495.0 (M+1). Prepared to afford a yellow solid after purification by chromatography on silica gel eluting with EtOAc-hexane solvent mixture

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

Procedure: Prepared according to Procedure K, Method 1 using 4-chloro-7-fluoro-2-(2-fluorophenyl)-3-methylquinoline (118 mg, 407 μmol), 5-bromo-2-morpholinobenzenamine (105 mg, 407 μmol) and 4.0N hydrochloric acid (0.10 mL, 407 μmol) in 1,4-dioxane in MeOH (1.00 mL) to afford a yellow solid after purification by chromatography on silica gel, eluting with EtOAc-DCM-hexane solvent mixture. Mass Spectrum (ESI) m/e=510.0 & 512.0 (M+1). Prepared to afford a yellow solid after purification by chromatography on silica gel eluting with EtOAc-DCM-hexane solvent mixture

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

Procedure: To a solution of 4-(4-bromo-2-nitrophenyl)morpholine (13.2 g, 46 mmol) dissolved in EtOAc (200.00 mL, 2043 mmol) at rt was added all in one portion tin(II) chloride dehydrate (52 g, 230 mmol). An exotherm developed and the orange color faded to a faint yellow. The reaction was stirred at ambient temperature for 15 min then heated to reflux for 45 min. After 60 min TLC indicated no starting material remained and the reaction was equilibrated to rt. The reaction was washed with 200 mL 5N aq. Sodium hydroxide solution followed by 100 mL water and 50 mL brine. The organic separation was stirred over anhydrous magnesium sulfate, filtered and the filtrate concd under reduced pressure to afford a pale yellow solid. Mass Spectrum (ESI) m/e=257.0 & 259.0 (M+1). then heated to reflux for 45 min After 60 min TLC indicated was equilibrated to rt The reaction was washed with 200 mL 5N aq. Sodium hydroxide solution The organic separation was stirred over anhydrous magnesium sulfate filtered the filtrate concd under reduced pressure to afford a pale yellow solid