N-(2,2,2-trifluoroethyl)sulfamoyl chloride

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

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

Procedure: 2,2,2-Trifluoroethylsulfamoyl chloride (53 mg, 0.3 mmol) was added dropwise to a stirred solution of the amine from Step 4 (50 mg, 0.2 mmol) and Et3N (37 μL, 0.3 mmol) in CH2Cl2 (2 m]L) at RT under N2. The mixture was stirred at RT overnight and then diluted with CH2Cl2 (25 mL), washed with NaHCO3 solution (20 m L), dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by column chromatography on silica eluting with 20% EtOAc/iso-hexane to yield the title sulfamide (5 mg, 6%). 1H NMR (CDCl3, 500 MHz) δ 8.02 (1H, s), 7.69 (1H, d, J=6.6 Hz), 7.45-7.42 (4H, m), 7.18 (2H, t, J=8.6 Hz), 6.58 (1H, s), 4.70 (1H, s), 4.30-4.27 (1H, m), 3.90 (3H, s), 3.57-3.53 (2H, m), 1.80 (6H, s). MS (ES+) C21H22F4N4O2S requires: 470, found: 471 (M+H+, 100%). washed with NaHCO3 solution (20 m L) dried (MgSO4) concentrated under reduced pressure The crude product was purified by column chromatography on silica eluting with 20% EtOAc/iso-hexane

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

Procedure: 2,2,2-Trifluoroethylsulfamoyl chloride (53 mg, 0.3 mmol) was added dropwise to a stirred solution of the amine from Step 4 (50 mg, 0.2 mmol) and Et3N (37 μL, 0.3 mmol) in CH2Cl2 (2 m]L) at RT under N2. The mixture was stirred at RT overnight and then diluted with CH2Cl2 (25 mL), washed with NaHCO3 solution (20 m L), dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by column chromatography on silica eluting with 20% EtOAc/iso-hexane to yield the title sulfamide (5 mg, 6%). 1H NMR (CDCl3, 500 MHz) δ 8.02 (1H, s), 7.69 (1H, d, J=6.6 Hz), 7.45-7.42 (4H, m), 7.18 (2H, t, J=8.6 Hz), 6.58 (1H, s), 4.70 (1H, s), 4.30-4.27 (1H, m), 3.90 (3H, s), 3.57-3.53 (2H, m), 1.80 (6H, s). MS (ES+) C21H22F4N4O2S requires: 470, found: 471 (M+H+, 100%). washed with NaHCO3 solution (20 m L) dried (MgSO4) concentrated under reduced pressure The crude product was purified by column chromatography on silica eluting with 20% EtOAc/iso-hexane

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

Procedure: This amine was dissolved in CH2Cl2 (5 mL) and treated with 2,2,2-trifluoroethylsulfamoyl chloride (91 mg, 0.45 mmol) and Et3N (63 μL, 0.45 mmol) and stirred at RT for 30 min. The solvent was evaporated under reduced pressure and the residue purified by silica chromatography eluting with 2% MeOH/CH2Cl2 to yield the title sulfamide as a colourless gum (18 mg, 23% over 2 steps). 1H NMR (CDCl3, 500 MHz) δ 7.80-7.76 (1H, s), 7.65 (1H, d, J=7.8 Hz), 7.38 (1H, t, J=7.8 Hz), 7.23 (1H, d, J=7.8 Hz), 7.18-7.10 (2H, m), 6.98 (2H, t, J=8.7 Hz), 6.35 (1H, s), 4.66-4.56 (2H, m), 4.38-4.28 (1H, m), 3.69 (3H, s), 3.53-3.42 (1H, m), 3.42-3.30 (1H, m), 3.02-2.84 (4H, m), 1.62-1.52 (3H, m). MS (ES+) C22H24F4N4O2S requires: 484, found: 485 (M+H+). The solvent was evaporated under reduced pressure the residue purified by silica chromatography eluting with 2% MeOH/CH2Cl2

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

Procedure: Prepared by the procedure of Example 1 Step 3 using the amine from Step 3 (72 mg, 0.20 mmol), Et3N (114 μL, 0.82 mmol) and 2,2,2-trifluoroethylsulfamoyl chloride (121 mg, 0.61 mmol) to yield, after purification by column chromatography on silica using 80-100% Et2O/iso-hexanes the title sulfamide (23 mg, 22%). 1H NMR (CDCl3, 500 MHz) δ 7.54 (1H, d, J=7.8 Hz), 7.48 (1H, t, J=7.8 Hz), 7.42 (1H, s), 7.23 (1H, d, J=7.5 Hz), 7.19 (2H, dd, J=8.5, 5.6 Hz), 6.97 (2H, t, J=8.5 Hz), 4.71 (1H, s), 4.43 (1H, t, J=7.4 Hz), 3.74 (3H, s), 3.57 (2H, quintet, J=7.4 Hz), 2.98-2.92 (2H, m), 2.87-2.82 (2H, m), 1.87 (3H, s), 1.79 (6H, s). MS (ES+) C24H28F4N4O2S requires: 512, found: 513 (M+H+, 100%). to yield after purification by column chromatography on silica using 80-100% Et2O/iso-hexanes the title sulfamide (23 mg, 22%)

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

Procedure: Prepared by the procedure of Example 1 Step 3. The amine from Step 3 (67 mg, 0.19 mmol), Et3N (80 □L, 0.57 mmol) and 2,2,2-trifluoroethylsulfamoyl chloride (75 mg, 0.38 mmol) were reacted to yield after purification by column chromatography on silica using 80% Et2O/iso-hexanes the title sulfamide (25 mg, 26%). 1H NMR (CDCl3, 500 MHz) δ 7.57-7.49 (2H, m), 7.45 (1H, t, J=7.8 Hz), 7.30 (1H, d, J=7.8 Hz), 7.19 (2H, dd, J=8.7, 5.6 Hz), 6.97 (2H, t J=8.7 Hz), 6.03 (1H, s), 4.69 (1H, s), 4.39 (1H, t, J=5.4 Hz), 4.10 (2H, q, J=7.2 Hz), 3.57 (2H, quintet, J=5.4 Hz), 3.03-2.90 (4H, m), 1.78 (6H, s), 1.39 (3H, t, J=7.2 Hz). MS (ES+) C24H28F4N4O2S requires: 512, found: 513 (M+H+, 100%). Prepared by the procedure of Example 1 Step 3 to yield after purification by column chromatography on silica using 80% Et2O/iso-hexanes the title sulfamide (25 mg, 26%)

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

Procedure: Prepared by the procedure of Example 1 Step 3. The amine from Step 3 (67 mg, 0.19 mmol), Et3N (80 □L, 0.57 mmol) and 2,2,2-trifluoroethylsulfamoyl chloride (75 mg, 0.38 mmol) were reacted to yield after purification by column chromatography on silica using 80% Et2O/iso-hexanes the title sulfamide (25 mg, 26%). 1H NMR (CDCl3, 500 MHz) δ 7.57-7.49 (2H, m), 7.45 (1H, t, J=7.8 Hz), 7.30 (1H, d, J=7.8 Hz), 7.19 (2H, dd, J=8.7, 5.6 Hz), 6.97 (2H, t J=8.7 Hz), 6.03 (1H, s), 4.69 (1H, s), 4.39 (1H, t, J=5.4 Hz), 4.10 (2H, q, J=7.2 Hz), 3.57 (2H, quintet, J=5.4 Hz), 3.03-2.90 (4H, m), 1.78 (6H, s), 1.39 (3H, t, J=7.2 Hz). MS (ES+) C24H28F4N4O2S requires: 512, found: 513 (M+H+, 100%). Prepared by the procedure of Example 1 Step 3 to yield after purification by column chromatography on silica using 80% Et2O/iso-hexanes the title sulfamide (25 mg, 26%)

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

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

Procedure: 2,2,2-Trifluoroethylsulfamoyl chloride (53 mg, 0.3 mmol) was added dropwise to a stirred solution of the amine from Step 4 (50 mg, 0.2 mmol) and Et3N (37 μL, 0.3 mmol) in CH2Cl2 (2 m]L) at RT under N2. The mixture was stirred at RT overnight and then diluted with CH2Cl2 (25 mL), washed with NaHCO3 solution (20 m L), dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by column chromatography on silica eluting with 20% EtOAc/iso-hexane to yield the title sulfamide (5 mg, 6%). 1H NMR (CDCl3, 500 MHz) δ 8.02 (1H, s), 7.69 (1H, d, J=6.6 Hz), 7.45-7.42 (4H, m), 7.18 (2H, t, J=8.6 Hz), 6.58 (1H, s), 4.70 (1H, s), 4.30-4.27 (1H, m), 3.90 (3H, s), 3.57-3.53 (2H, m), 1.80 (6H, s). MS (ES+) C21H22F4N4O2S requires: 470, found: 471 (M+H+, 100%). washed with NaHCO3 solution (20 m L) dried (MgSO4) concentrated under reduced pressure The crude product was purified by column chromatography on silica eluting with 20% EtOAc/iso-hexane

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

Procedure: This amine was dissolved in CH2Cl2 (5 mL) and treated with 2,2,2-trifluoroethylsulfamoyl chloride (91 mg, 0.45 mmol) and Et3N (63 μL, 0.45 mmol) and stirred at RT for 30 min. The solvent was evaporated under reduced pressure and the residue purified by silica chromatography eluting with 2% MeOH/CH2Cl2 to yield the title sulfamide as a colourless gum (18 mg, 23% over 2 steps). 1H NMR (CDCl3, 500 MHz) δ 7.80-7.76 (1H, s), 7.65 (1H, d, J=7.8 Hz), 7.38 (1H, t, J=7.8 Hz), 7.23 (1H, d, J=7.8 Hz), 7.18-7.10 (2H, m), 6.98 (2H, t, J=8.7 Hz), 6.35 (1H, s), 4.66-4.56 (2H, m), 4.38-4.28 (1H, m), 3.69 (3H, s), 3.53-3.42 (1H, m), 3.42-3.30 (1H, m), 3.02-2.84 (4H, m), 1.62-1.52 (3H, m). MS (ES+) C22H24F4N4O2S requires: 484, found: 485 (M+H+). The solvent was evaporated under reduced pressure the residue purified by silica chromatography eluting with 2% MeOH/CH2Cl2

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

Procedure: Prepared by the procedure of Example 1 Step 3 using the amine from Step 3 (72 mg, 0.20 mmol), Et3N (114 μL, 0.82 mmol) and 2,2,2-trifluoroethylsulfamoyl chloride (121 mg, 0.61 mmol) to yield, after purification by column chromatography on silica using 80-100% Et2O/iso-hexanes the title sulfamide (23 mg, 22%). 1H NMR (CDCl3, 500 MHz) δ 7.54 (1H, d, J=7.8 Hz), 7.48 (1H, t, J=7.8 Hz), 7.42 (1H, s), 7.23 (1H, d, J=7.5 Hz), 7.19 (2H, dd, J=8.5, 5.6 Hz), 6.97 (2H, t, J=8.5 Hz), 4.71 (1H, s), 4.43 (1H, t, J=7.4 Hz), 3.74 (3H, s), 3.57 (2H, quintet, J=7.4 Hz), 2.98-2.92 (2H, m), 2.87-2.82 (2H, m), 1.87 (3H, s), 1.79 (6H, s). MS (ES+) C24H28F4N4O2S requires: 512, found: 513 (M+H+, 100%). to yield after purification by column chromatography on silica using 80-100% Et2O/iso-hexanes the title sulfamide (23 mg, 22%)

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

Procedure: Prepared by the procedure of Example 1 Step 3. The amine from Step 3 (67 mg, 0.19 mmol), Et3N (80 □L, 0.57 mmol) and 2,2,2-trifluoroethylsulfamoyl chloride (75 mg, 0.38 mmol) were reacted to yield after purification by column chromatography on silica using 80% Et2O/iso-hexanes the title sulfamide (25 mg, 26%). 1H NMR (CDCl3, 500 MHz) δ 7.57-7.49 (2H, m), 7.45 (1H, t, J=7.8 Hz), 7.30 (1H, d, J=7.8 Hz), 7.19 (2H, dd, J=8.7, 5.6 Hz), 6.97 (2H, t J=8.7 Hz), 6.03 (1H, s), 4.69 (1H, s), 4.39 (1H, t, J=5.4 Hz), 4.10 (2H, q, J=7.2 Hz), 3.57 (2H, quintet, J=5.4 Hz), 3.03-2.90 (4H, m), 1.78 (6H, s), 1.39 (3H, t, J=7.2 Hz). MS (ES+) C24H28F4N4O2S requires: 512, found: 513 (M+H+, 100%). Prepared by the procedure of Example 1 Step 3 to yield after purification by column chromatography on silica using 80% Et2O/iso-hexanes the title sulfamide (25 mg, 26%)