3-(4-bromophenyl)-N-methylpropanamide

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

Procedure: Add oxalyl chloride (1.75 mL, 2.54 g, 4 eq.) to a solution of 3-(4-bromo-phenyl)-propionic acid in methylene chloride (100 mL), which contains 0.1 mL DMF at 0° C. and allow the reaction mixture to warm to room temperature and stir 1 hour. Evaporate solvent and dissolve it in 10 mL THF. Add half of the THF solution to 20 mL of methylamine (2M) and stir another hour. Add water to the solution to dissolve solid and wash organic layer with 2N HCl, water and saturated aq. sodium chloride and dry it over MgSO4. Evaporate solvent to afford the title compound 500 mg, 41%. MS 246.0. at 0° C. stir another hour wash organic layer with 2N HCl, water and saturated aq. sodium chloride dry it over MgSO4

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

Procedure: Using a procedure analogous to that used to prepare 22A, 2-(4-bromophenyl)acetic acid (1.6 g, 7.0 mmol) was coupled to methylamine to yield 23A (2.0 g, 75%) as a white solid. MS (ESI) m/z 228.20/230.20 (M+H)+.

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

Procedure: Borane in THF (1.0 M, 28 mL, 28 mmol) was added dropwise to a solution of 22A (1.6 g, 7.0 mmol) in THF (17.5 mL). After stirring the reaction mixture for 30 min at 0° C. the mixture was refluxed for 4 h. Methanol (20 mL) was added to the mixture at 0° C. followed by the addition of 20 mL 6.0 M HCl dropwise. After refluxing for 30 min the volatiles were removed in vacuo. 50% NaOH (12 mL) was added dropwise while maintaining the temperature below 30° C. The resulting mixture was diluted with water (100 mL) and extracted with diethyl ether (3×100 mL). The organics were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 22B (1.57 g, 97%) as a clear oil. MS (ESI) m/z 227.99/229.99 (M+H)+. was refluxed for 4 h After refluxing for 30 min the volatiles were removed in vacuo 50% NaOH (12 mL) was added dropwise while maintaining the temperature below 30° C The resulting mixture was diluted with water (100 mL) extracted with diethyl ether (3×100 mL) washed with brine dried over Na2SO4 concentrated in vacuo

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

Procedure: Borane in THF (1.0 M, 28 mL, 28 mmol) was added dropwise to a solution of 22A (1.6 g, 7.0 mmol) in THF (17.5 mL). After stirring the reaction mixture for 30 min at 0° C. the mixture was refluxed for 4 h. Methanol (20 mL) was added to the mixture at 0° C. followed by the addition of 20 mL 6.0 M HCl dropwise. After refluxing for 30 min the volatiles were removed in vacuo. 50% NaOH (12 mL) was added dropwise while maintaining the temperature below 30° C. The resulting mixture was diluted with water (100 mL) and extracted with diethyl ether (3×100 mL). The organics were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 22B (1.57 g, 97%) as a clear oil. MS (ESI) m/z 227.99/229.99 (M+H)+. was refluxed for 4 h After refluxing for 30 min the volatiles were removed in vacuo 50% NaOH (12 mL) was added dropwise while maintaining the temperature below 30° C The resulting mixture was diluted with water (100 mL) extracted with diethyl ether (3×100 mL) washed with brine dried over Na2SO4 concentrated in vacuo

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

Procedure: EDAC (1.56 g, 8.1 mmol) was added in one portion to 3-(4-bromophenyl)propanoic acid (2.5 g, 7.4 mmol) and HOBt (1.1 g, 8.1 mmol) in DMF (6 mL) and the reaction mixture was stirred for 2 h. The reaction mixture was cooled to 0° C. and NH2Me (2.0 M in MeOH, 29 mL, 58 mmol) was added dropwise. The solution was stirred at 0° C. for 30 min and 10 h at ambient temperature. The reaction mixture was diluted with water (25 mL), extracted with diethyl either (3×50 mL). The combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 22A (1.7 g, 67%) as an off-white solid. MS (ESI) m/z 242.22/244.22 (M+H)+. The solution was stirred at 0° C. for 30 min and 10 h at ambient temperature extracted with diethyl either (3×50 mL) The combined organics were washed with brine dried over Na2SO4 concentrated in vacuo

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

Procedure: Add oxalyl chloride (1.75 mL, 2.54 g, 4 eq.) to a solution of 3-(4-bromo-phenyl)-propionic acid in methylene chloride (100 mL), which contains 0.1 mL DMF at 0° C. and allow the reaction mixture to warm to room temperature and stir 1 hour. Evaporate solvent and dissolve it in 10 mL THF. Add half of the THF solution to 20 mL of methylamine (2M) and stir another hour. Add water to the solution to dissolve solid and wash organic layer with 2N HCl, water and saturated aq. sodium chloride and dry it over MgSO4. Evaporate solvent to afford the title compound 500 mg, 41%. MS 246.0. at 0° C. stir another hour wash organic layer with 2N HCl, water and saturated aq. sodium chloride dry it over MgSO4

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

Procedure: Using a procedure analogous to that used to prepare 22A, 2-(4-bromophenyl)acetic acid (1.6 g, 7.0 mmol) was coupled to methylamine to yield 23A (2.0 g, 75%) as a white solid. MS (ESI) m/z 228.20/230.20 (M+H)+.

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

Procedure: Borane in THF (1.0 M, 28 mL, 28 mmol) was added dropwise to a solution of 22A (1.6 g, 7.0 mmol) in THF (17.5 mL). After stirring the reaction mixture for 30 min at 0° C. the mixture was refluxed for 4 h. Methanol (20 mL) was added to the mixture at 0° C. followed by the addition of 20 mL 6.0 M HCl dropwise. After refluxing for 30 min the volatiles were removed in vacuo. 50% NaOH (12 mL) was added dropwise while maintaining the temperature below 30° C. The resulting mixture was diluted with water (100 mL) and extracted with diethyl ether (3×100 mL). The organics were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 22B (1.57 g, 97%) as a clear oil. MS (ESI) m/z 227.99/229.99 (M+H)+. was refluxed for 4 h After refluxing for 30 min the volatiles were removed in vacuo 50% NaOH (12 mL) was added dropwise while maintaining the temperature below 30° C The resulting mixture was diluted with water (100 mL) extracted with diethyl ether (3×100 mL) washed with brine dried over Na2SO4 concentrated in vacuo

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

Procedure: EDAC (1.56 g, 8.1 mmol) was added in one portion to 3-(4-bromophenyl)propanoic acid (2.5 g, 7.4 mmol) and HOBt (1.1 g, 8.1 mmol) in DMF (6 mL) and the reaction mixture was stirred for 2 h. The reaction mixture was cooled to 0° C. and NH2Me (2.0 M in MeOH, 29 mL, 58 mmol) was added dropwise. The solution was stirred at 0° C. for 30 min and 10 h at ambient temperature. The reaction mixture was diluted with water (25 mL), extracted with diethyl either (3×50 mL). The combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 22A (1.7 g, 67%) as an off-white solid. MS (ESI) m/z 242.22/244.22 (M+H)+. The solution was stirred at 0° C. for 30 min and 10 h at ambient temperature extracted with diethyl either (3×50 mL) The combined organics were washed with brine dried over Na2SO4 concentrated in vacuo