4-bromo-2-chlorobenzenesulfonyl chloride

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

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

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

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

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

Procedure: To a solution of 4-bromo-2-chlorobenzenesulfonyl chloride (2.50 g, 8.45 mmol) in THF (25 ml) was added a solution of ammonia (25%, 6.3 ml, 84.5 mmol). The reaction mixture was stirred for 4 h at RT. Ethyl acetate (70 ml) and water (50 mL) were added. The organic phase was separated and washed with hydrochloric acid (1 M, 50 ml) and brine (2×30 ml) and dried over sodium sulfate. After evaporation the product was obtained as a white solid (2.05 g, 90%) which was used in the next step without further purification. The organic phase was separated washed with hydrochloric acid (1 M, 50 ml) and brine (2×30 ml) dried over sodium sulfate After evaporation the product

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

Procedure: Hydrazine monohydrate (1.51 mL, 48 mmol) was added to a cooled 0° C. solution of 4-bromo-2-chlorobenzenesulfonyl chloride (5 g, 17.2 mmol) dissolved in THF (50 mL). The reaction was stirred at room temperature for 2 hours and then the solvent was removed in vacuo to give a white solid. The solid was dissolved in EtOH (100 mL) and treated with sodium acetate (6.56 g, 80 mmol) followed by methyl iodide (4.9 mL, 79 mmol). The reaction mixture was refluxed for 18 hours. The solvent was removed in vacuo to give a residue that was partitioned between 1 N HCl and EtOAc. The organic layer was dried over MgSO4 and concentrated. The crude mixture was purified by flash column chromatography to give the product (1.5 g, 32%). 1H NMR (300 MHz, CDCl3): δ 3.26 (s, 3 H), 7.63 (dd, J=8.5, 1.9 Hz, 2 H), 7.74 (d, J=1.9 Hz, 1 H), 8.02 (d, J=8.5 Hz, 1 H). the solvent was removed in vacuo to give a white solid The reaction mixture was refluxed for 18 hours The solvent was removed in vacuo to give a residue that was partitioned between 1 N HCl and EtOAc The organic layer was dried over MgSO4 concentrated The crude mixture was purified by flash column chromatography

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

Procedure: Using a method analogous to Method E, using 4-bromo-2-chlorobenzenesulfonyl chloride and 3-aminobenzenesulfonamide, the title compound was obtained as a white solid.

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

Procedure: A solution of 5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)aniline (D4) (1.20 g, 5.09 mmol) in dichloromethane (35 ml) was treated with morpholinomethyl-polystyrene HL resin (2.43 g, 4.2 mmol/g loading, 10.21 mmol) and then the 4-bromo-2-chlorobenzenesulfonyl chloride (2.96 g, 10.21 mmol). The resulting solution was stirred at room temperature overnight. The resin and was filtered, washed with methanol, and the solvent evaporated in vacuo. The residue was then passed through an SCX column eluting first with methanol followed by 2M ammonia in methanol. The basic fractions were collectedand solvent evaporated in vacuo to afford a crude product which was purified further by chromatography using a Flashmaster using an elution gradient of 0 to 5% methanol in dichloromethane. The relevant fractions were collected, combined and the solvent evaporated in vacuo to afford the title compound (E104). MS (ES+) m/e 488/490/492 [M+H]+. The resin and was filtered washed with methanol the solvent evaporated in vacuo eluting first with methanol evaporated in vacuo to afford a crude product which was purified further by chromatography The relevant fractions were collected the solvent evaporated in vacuo

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Aminomethyl-N-tert-butyl-2-chloro-benzenesulfonamide was synthesized in a manner analogous to 4-Aminomethyl-N-tert-butyl-3-methyl-benzenesulfonamide in Example 4, using 4-bromo-2-chlorobenzene-1-sulfonyl chloride in place of 4-bromo-3-methylbenzene-1-sulfonyl chloride. In the second step NMP was used as the solvent, Pd(dppf)Cl2 alone was used as catalyst and the reaction mixture was stirred at 150° C. for 30 min, then heated at 120° C. overnight. Reduction of the cyano group to aminomethyl group in the last step was achieved by stirring with lithium aluminium hydride from 0° C. to room temperature in THF. heated at 120° C. overnight

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

Procedure: Using a method analogous to Method E, using 4-bromo-2-chlorobenzenesulfonyl chloride and 3-aminobenzenesulfonamide, the title compound was obtained as a white solid.

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

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