cyclohexanesulfonamide

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

Procedure: Following the procedure for the preparation of cyclohexylsulfonamide, 49 mL (37 mmol) of 0.75M neopentylmagnesium chloride (Alfa) in diethyl ether was converted to 1.52 g (27%) of the desired product as a white solid. 1H NMR (CDCl3) δ 1.17 (s, 9H), 3.12 (s, 2H), 4.74 (brs, 2H); 13C NMR (CDCl3) δ 29.46, 31.51, 67.38; MS m/e 150 (M−1)−.

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

Procedure: Following the procedure for the preparation of cyclohexylsulfonamide, 49 mL (37 mmol) of 0.75M neopentylmagnesium chloride (Alfa) in diethyl ether was converted to 1.52 g (27%) of the desired product as a white solid. 1H NMR (CDCl3) δ 1.17 (s, 9H), 3.12 (s, 2H), 4.74 (brs, 2H); 13C NMR (CDCl3) δ 29.46, 31.51, 67.38; MS m/e 150 (M−1)−.

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

Procedure: Following the procedure for the preparation of cyclohexylsulfonamide, 49 mL (37 mmol) of 0.75M neopentylmagnesium chloride (Alfa) in diethyl ether was converted to 1.52 g (27%) of the desired product as a white solid. 1H NMR (CDCl3) δ 1.17 (s, 9H), 3.12 (s, 2H), 4.74 (brs, 2H); 13C NMR (CDCl3) δ 29.46, 31.51, 67.38; MS m/e 150 (M−1)−.

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

Procedure: Following the procedure for the preparation of cyclohexylsulfonamide, 49 mL (37 mmol) of 0.75M neopentylmagnesium chloride (Alfa) in diethyl ether was converted to 1.52 g (27%) of the desired product as a white solid. 1H NMR (CDCl3) δ 1.17 (s, 9H), 3.12 (s, 2H), 4.74 (brs, 2H); 13C NMR (CDCl3) δ 29.46, 31.51, 67.38; MS m/e 150 (M−1)−.

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

Procedure: 2-(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-N-(4-fluoro-benzyl)-N-methoxy-acetamide was treated with cyclohexanesulfonic acid amide as described in the preparation of compound 1 to yield the title compound. LCMS (M+H) calcd for C18H24FN2O6S: 415.1; found: 415.0. 1H NMR (500 MHz, CDCl3) δ: 1.19 (overlapping m, 30,1.63 (overlapping m, 3), 1.90 (br m, 2), 2.17 (m, 2), 3.51 (m, 1), 3.69 (s, 3), 4.78 (s, 2), 6.53 (s, 1), 7.00 (m, 2), 7.26 (m, 2).

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

Procedure: To a solution of intermediate 5 from Example 344 (700 mg, 2.7 mmol) in THF (90 mL), methanol (50 mL) and water (12 mL) mixture, lithium hydroxide monohydrate (1700 mg, 2.0 mmol) was added. The reaction mixture was stirred at rt. for overnight. Then it was acidified with 1N HCl solution to pH=3 to 5. Extracted with ethyl acetate (2×20 mL) and the organic layers were combined and dried (MgSO4). Evaporation of solvent gave thick colorless oil as product (intermediate 7) (0.58, 88% yield). Extracted with ethyl acetate (2×20 mL) dried (MgSO4) Evaporation of solvent

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

Procedure: The general method of procedure A was followed with cyclohexanesulfonamide (1.89 g), acetone (5 ml), 1N sodium hydroxide (11.6 ml). After stirring overnight at room temperature, the mixture was cooled in an ice bath and 4-chlorophenyl isocyanate (1.89 g) dissolved in acetone (5 ml) was added. The mixture was warmed to room temperature and stirred two days, filtered, and the separated white solid washed with water. The filtrates were combined and treated with glacial acetic acid (1 ml) followed by addition of water. The resulting solid was collected by filtration, washed with water and air dried to provide 2.57 g of a tan powder. the mixture was cooled in an ice bath was added The mixture was warmed to room temperature stirred two days filtered the separated white solid washed with water treated with glacial acetic acid (1 ml) followed by addition of water The resulting solid was collected by filtration washed with water and air dried

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

Procedure: The general method of procedure A was followed with cyclohexanesulfonamide (1.89 g), acetone (5 ml), 1N sodium hydroxide (11.6 ml). After stirring overnight at room temperature, the mixture was cooled in an ice bath and 4-chlorophenyl isocyanate (1.89 g) dissolved in acetone (5 ml) was added. The mixture was warmed to room temperature and stirred two days, filtered, and the separated white solid washed with water. The filtrates were combined and treated with glacial acetic acid (1 ml) followed by addition of water. The resulting solid was collected by filtration, washed with water and air dried to provide 2.57 g of a tan powder. the mixture was cooled in an ice bath was added The mixture was warmed to room temperature stirred two days filtered the separated white solid washed with water treated with glacial acetic acid (1 ml) followed by addition of water The resulting solid was collected by filtration washed with water and air dried

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

Procedure: Following the procedure for the preparation of cyclohexylsulfonamide, 49 mL (37 mmol) of 0.75M neopentylmagnesium chloride (Alfa) in diethyl ether was converted to 1.52 g (27%) of the desired product as a white solid. 1H NMR (CDCl3) δ 1.17 (s, 9H), 3.12 (s, 2H), 4.74 (brs, 2H); 13C NMR (CDCl3) δ 29.46, 31.51, 67.38; MS m/e 150 (M−1)−.

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 1 of Example 103 from 4-[(1S)-1-({[5-chloro-2-(4-fluorophenoxy)pyridin-3-yl]carbonyl}amino)ethyl]benzoic acid (step 5 of Example 44) and cyclohexanesulfonamide (Helv. Chim. Acta 1975, 58, 2321): 1H-NMR (CDCl3) δ 8.53 (1H, d, J=2.6 Hz), 8.14 (1H, d, J=2.6 Hz), 8.15–8.08 (1H, m), 7.81 (2H, d, J=8.3 Hz), 7.49 (2H, d, J=8.3 Hz), 7.22–7.10 (4H, m), 5.42–5.30 (1H, m), 3.80–3.65 (1H, m), 2.26–2.16 (2H, m), 1.98–1.85 (2H, m), 1.78–1.50 (4H, m), 1.60 (3H, d, J=7.0 Hz), 1.43–1.15 (2H, m); MS (ESI) m/z 560 (M+H)+, 558 (M−H)−.

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

Procedure: To a suspension of cyclohexanesulfonic acid sodium salt (2.5 g) in DMF (15 mL) was added thionyl chloride (1.96 mL) under ice-cooling, and the mixture was stirred at room temperature for 29 hr. The reaction mixture was added to a mixture of ice-cooled water (100 mL) and toluene (100 mL), and the mixture was extracted. The organic layer was concentrated under reduced pressure. THF (50 mL) was added to the residue, 28% aqueous ammonia (10 mL) was added dropwise to the solution under ice-cooling, and the mixture was stirred at room temperature for 17 hr. After concentration under reduced pressure, water (100 mL) and ethyl acetate (100 mL) were added to extract the residue. The organic layer was concentrated under reduced pressure to give the title compound (760 mg) as a white solid. cooling The reaction mixture was added to a mixture of ice- the mixture was extracted The organic layer was concentrated under reduced pressure THF (50 mL) was added to the residue, 28% aqueous ammonia (10 mL) was added dropwise to the solution under ice- cooling the mixture was stirred at room temperature for 17 hr After concentration under reduced pressure, water (100 mL) and ethyl acetate (100 mL) were added to extract the residue The organic layer was concentrated under reduced pressure

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

Procedure: According to Reference Example 9-19, by use of cyclohexanesulfonyl chloride (300 mg, 1.6 mmol) and a 25% aqueous ammonia solution (2 mL), the mixture was stirred and reacted at room temperature for 18 hours. Then, purification by silica gel column chromatography (chloroform/methanol=1/0 to 20/1) was performed to give cyclohexanesulfonamide (Compound FW) (161 mg, yield: 60%). reacted at room temperature for 18 hours Then, purification by silica gel column chromatography (chloroform/methanol=1/0 to 20/1)