3-chlorobenzenesulfonamide

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

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

Procedure: A mixture of 3,4-dibromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-pyrrolo[2,3-b]pyridine (D3) (1.020 g, 2.51 mmol), xantphos (0.218 g, 0.377 mmol), palladium(II) acetate (0.042 g, 0.188 mmol), cesium carbonate (1.636 g, 5.02 mmol) and 3-chlorobenzenesulfonamide (0.602 g, 3.14 mmol) in 1,4-dioxane (15 mL) was stirred at 100° C. for ca. 3 hours. The mixture was evaporated to dryness and the residues partitioned between water (15 mL) and ethyl acetate (40 mL). The aqueous phase was separated and extracted with additional ethyl acetate (15 mL). The organic extracts were combined, washed with brine (10 mL), dried with MgSO4 and evaporated to dryness. The residue was purified through silica gel, eluting with a gradient of 0-40% ethyl acetate in cyclohexane to give the title compound (407.4 mg). LCMS (A): m/z (M−H)− 514/516, C19H23BrClN3O3SSi requires 515/517 (acidic). The mixture was evaporated to dryness the residues partitioned between water (15 mL) and ethyl acetate (40 mL) The aqueous phase was separated extracted with additional ethyl acetate (15 mL) washed with brine (10 mL) dried with MgSO4 evaporated to dryness The residue was purified through silica gel eluting with a gradient of 0-40% ethyl acetate in cyclohexane

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

Procedure: The title compound was prepared according to the procedure described in step 2 of Example 18 from 2-[4-(2-ethyl-4-phenyl-1H-imidazol-1-yl)phenyl]ethylcarbamate and 3-chlorobenzenesulfonamide. MS (ESI) m/z 509 [M+H]+, 507 [M−H]−, 1H-NMR (CDCl3)δ1.22 (3H, t, J=7.5 Hz), 2.68 (2H, q, J=7.5 Hz), 2.86 (2H, t, J=6.6 Hz), 3.47-3.56 (2H, m), 6.44 (1H, br), 7.23-7.28 (5H, m), 7.36 (2H, t, J=7.3 Hz), 7.45 (2H, t, J=8.1 Hz), 7.58 (2H, d, J=8.1 Hz), 7.73-7.78 (2H, m), 7.87 (1H, m).

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

Procedure: The title compound was prepared according to the procedure described in step 2 of Example 18 from 2-[4-(2-ethyl-4-phenyl-1H-imidazol-1-yl)phenyl]ethylcarbamate and 3-chlorobenzenesulfonamide. MS (ESI) m/z 509 [M+H]+, 507 [M−H]−, 1H-NMR (CDCl3)δ1.22 (3H, t, J=7.5 Hz), 2.68 (2H, q, J=7.5 Hz), 2.86 (2H, t, J=6.6 Hz), 3.47-3.56 (2H, m), 6.44 (1H, br), 7.23-7.28 (5H, m), 7.36 (2H, t, J=7.3 Hz), 7.45 (2H, t, J=8.1 Hz), 7.58 (2H, d, J=8.1 Hz), 7.73-7.78 (2H, m), 7.87 (1H, m).

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

Procedure: The title compound was prepared according to the procedure described in step 2 of Example 22 from phenyl 2-[4-(3,5-dimethyl-4-phenyl-1H-pyrazol-1-yl)phenyl]ethylcarbamate (step 1 of Example 22) and 3-chlorobenzenesulfonamide: 1H-NMR (CDCl3) δ 7.91-7.90 (1H, m), 7.83-7.79 (1H, m), 7.53-7.20 (11H, m), 6.32 (1H, br.s), 3.47-3.40 (2H, m), 2.81 (2H, t, J=6.6 Hz), 2.30 (3H, s), 2.22 (3H, s).

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

Procedure: A mixture of 4-chloro-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine (Description 43) (100 mg, 0.363 mmol), 3-chlorobenzensulfonamide (90 mg, 0.471 mmol), palladium(II) acetate (8.14 mg, 0.036 mmol), xantphos (42.0 mg, 0.073 mmol), and Cs2CO3 (236 mg, 0.725 mmol) in 1,4-dioxane (3.6 mL) was degassed with nitrogen for 5 min. The mixture was heated at 150° C. for 45 min in a microwave and then poured into water (50 mL) and extracted with DCM (30 mL×4). The organic layers were combined, washed with brine (50 mL), dried over MgSO4, filtered and evaporated in vacuo. The residue was purified by chromatography on silica, eluting with a gradient of 0-10% ethanol in toluene, followed by further purification by MDAP (basic conditions), to give the title compound (72 mg). LCMS (A) m/z: 431 [M+1]+, Rt 1.34 min (acidic). was degassed with nitrogen for 5 min poured into water (50 mL) extracted with DCM (30 mL×4) washed with brine (50 mL) dried over MgSO4 filtered evaporated in vacuo The residue was purified by chromatography on silica eluting with a gradient of 0-10% ethanol in toluene followed by further purification by MDAP (basic conditions)

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

Procedure: A mixture of 3,4-dibromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-pyrrolo[2,3-b]pyridine (D3) (1.020 g, 2.51 mmol), xantphos (0.218 g, 0.377 mmol), palladium(II) acetate (0.042 g, 0.188 mmol), cesium carbonate (1.636 g, 5.02 mmol) and 3-chlorobenzenesulfonamide (0.602 g, 3.14 mmol) in 1,4-dioxane (15 mL) was stirred at 100° C. for ca. 3 hours. The mixture was evaporated to dryness and the residues partitioned between water (15 mL) and ethyl acetate (40 mL). The aqueous phase was separated and extracted with additional ethyl acetate (15 mL). The organic extracts were combined, washed with brine (10 mL), dried with MgSO4 and evaporated to dryness. The residue was purified through silica gel, eluting with a gradient of 0-40% ethyl acetate in cyclohexane to give the title compound (407.4 mg). LCMS (A): m/z (M−H)− 514/516, C19H23BrClN3O3SSi requires 515/517 (acidic). The mixture was evaporated to dryness the residues partitioned between water (15 mL) and ethyl acetate (40 mL) The aqueous phase was separated extracted with additional ethyl acetate (15 mL) washed with brine (10 mL) dried with MgSO4 evaporated to dryness The residue was purified through silica gel eluting with a gradient of 0-40% ethyl acetate in cyclohexane

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

Procedure: A mixture of 3,4-dibromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-pyrrolo[2,3-b]pyridine (D3) (1.020 g, 2.51 mmol), xantphos (0.218 g, 0.377 mmol), palladium(II) acetate (0.042 g, 0.188 mmol), cesium carbonate (1.636 g, 5.02 mmol) and 3-chlorobenzenesulfonamide (0.602 g, 3.14 mmol) in 1,4-dioxane (15 mL) was stirred at 100° C. for ca. 3 hours. The mixture was evaporated to dryness and the residues partitioned between water (15 mL) and ethyl acetate (40 mL). The aqueous phase was separated and extracted with additional ethyl acetate (15 mL). The organic extracts were combined, washed with brine (10 mL), dried with MgSO4 and evaporated to dryness. The residue was purified through silica gel, eluting with a gradient of 0-40% ethyl acetate in cyclohexane to give the title compound (407.4 mg). LCMS (A): m/z (M−H)− 514/516, C19H23BrClN3O3SSi requires 515/517 (acidic). The mixture was evaporated to dryness the residues partitioned between water (15 mL) and ethyl acetate (40 mL) The aqueous phase was separated extracted with additional ethyl acetate (15 mL) washed with brine (10 mL) dried with MgSO4 evaporated to dryness The residue was purified through silica gel eluting with a gradient of 0-40% ethyl acetate in cyclohexane

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

Procedure: Prepared by coupling 1a and 3-chlorobenzenesulfonamide in accordance with Procedure 1, Method B described hereinabove. Yield (25%); 1H NMR (d6-DMSO) δ 12.36 (s, 1H), 7.88-7.76 (m, 3H), 7.63 (t, J=8.1 Hz, 1H), 7.42-7.07 (m, 13H), 6.84 (d, J=8.0 Hz, 2H), 6.40 (d, J=15.7 Hz, 1H), 2.36 (q, J=7.3 Hz, 2H), 0.82 (t, J=7.3 Hz, 3H); APcI m/z: 527 (M−H−). Prepared Yield (25%)

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

Procedure: Prepared by coupling 1a and 3-chlorobenzenesulfonamide in accordance with Procedure 1, Method B described hereinabove. Yield (25%); 1H NMR (d6-DMSO) δ 12.36 (s, 1H), 7.88-7.76 (m, 3H), 7.63 (t, J=8.1 Hz, 1H), 7.42-7.07 (m, 13H), 6.84 (d, J=8.0 Hz, 2H), 6.40 (d, J=15.7 Hz, 1H), 2.36 (q, J=7.3 Hz, 2H), 0.82 (t, J=7.3 Hz, 3H); APcI m/z: 527 (M−H−). Prepared Yield (25%)

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

Procedure: Prepared by coupling 1a and 3-chlorobenzenesulfonamide in accordance with Procedure 1, Method B described hereinabove. Yield (25%); 1H NMR (d6-DMSO) δ 12.36 (s, 1H), 7.88–7.76 (m, 3H), 7.63 (t, J=8.1 Hz, 1H), 7.42–7.07 (m, 13H), 6.84 (d, J=8.0 Hz, 2H), 6.40 (d, J=15.7 Hz, 1H), 2.36 (q, J=7.3 Hz, 2H), 0.82 (t, J=7.3 Hz, 3H); APcI m/z: 527 (M−H−). Prepared Yield (25%)

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

Procedure: 0.57 g (1 mol equiv.) 4-Ethyl-N-(2,2,2-trifluoro-ethyl)-4,5-dihydro-pyrazole-1-carboximidothioic acid methyl ester and 3.0 g (6.8 mol equiv.) 3-chloro-benzenesulfonamide were added to 20 mL acetonitrile. The reaction mixture was refluxed for 72 hours, and volatiles were removed under reduced pressure. The residue was taken up in ethyl acetate and extracted with 2N NaOH. The organic layer was dried over Na2SO4, filtered and evaporated to dryness. Purification by flash chromatography on silica gel (Et2O:PA=1:1) afforded 0.36 g (38%) 3-chloro-N-[(4-ethyl-4,5-dihydro-pyrazol-1-yl)-(2,2,2-trifluoro-ethylamino)-methylene]-benzenesulfonamide. 1H NMR (400 MHz, CDCl3) δ 1.00 (t, J=7.5 Hz, 3H), 1.51-1.74 (m, 2H), 3.16-3.27 (m, 1H), 3.87 (dd, J=11.2, 7.5 Hz, 1H), 4.03-4.14 (m, 2H), 4.28 (t, J=11.2 Hz, 1H), 7.03 (d, J=1.5 Hz, 1H), 7.41 (t, J=7.8 Hz, 1H), 7.46-7.50 (m, 1H), 7.79-7.84 (m, 1H), 7.91-7.94 (m, 1H). The reaction mixture was refluxed for 72 hours volatiles were removed under reduced pressure extracted with 2N NaOH The organic layer was dried over Na2SO4 filtered evaporated to dryness Purification by flash chromatography on silica gel (Et2O:PA=1:1)