Cyclopropanesulfonamide

White solid

II. Preparation of P1' Intermediates 1. Preparation of Cyclopropylsulfonamide Method 1 (of 2): To a solution of 100 mL of THF cooled to 0° C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to room temperature overnight and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiOTo a solution of 100 mL of THF cooled to 0° C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to room temperature overnight and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiOTo a solution of 100 mL of THF cooled to 0° C. was bubbled in gaseous ammonia until saturation was reached. To a solution of 100 mL of THF cooled to 0° C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30percent to 60percent EtOAc/Hexanes) to afford 3.45 g (100percent) of cyclopropyl sulfonamide as a white solid. To a solution of 100 mL of THF cooled to 0 C was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g(28. 45 mmol) of cyclopropylsulfonyl chloride (purchased from ArrayBiopharma) in 50mL of THF, the solution warmed to rtovernite and stirred one additional day. The mixture was concentrated until 1-2mL of solvent remained, applied onto 30 g plug ofSi02 (eluted with 30percent to 60percent EtOAc/Hexanes) to afford 3.45g (100percent) of cyclopropyl sulfonamide as a whitesolid.'H NMR (Methanol-d4) 0.94-1. 07 (m, 4H), 2.52-2. 60 (m, 1H); 13C NMR(methanol-d4)8 5.92, 33.01.Method A: To a solution of 100 mL of THF cooled to 0 °C was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied onto 30 g plug of Si02 (eluted with 30percent to 60percent EtOAc/Hexanes) to afford 3. 45g (100percent) of cyclopropyl sulfonamide as a white solid NMR (Methanol-d4) 8 0.94-1. 07 (m, 4H), 2.52-2. 60 (m, 1H) ; 13C NMR (methanol-d4) 8 5.92, 33.01.Method A:; O NHTo a solution of 100 mL of THF cooled to 0° C. was bubbled in gaseous ammonia until saturation was reached. Method A To a solution of 100 mL of THF cooled to 0° C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnight and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30percent to 60percent EtOAc/Hexanes) to afford 3.45 g (100percent) of cyclopropyl sulfonamide as a white solid. To a solution of 100 mL of THF cooled to 0° C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30percent to 60percent EtOAc/Hexanes) to afford 3.45 g (100percent) of cyclopropyl sulfonamide as a white solid. Method 2 To a solution of 100 mL of THF cooled to 0 Example 27Synthesis of new sulfonamides[0529] Preparation of compound 3: compound 1 (1Og, 71mmol) was dissolved in dry DCM (150ml) under nitrogen. The resulting solution was bubbled through NHCyclopropylsulfonyl chloride (5 g, 35.56 mmol) was dissolved in 0.5 M ammonia in dioxane (200 ml, 100 mmol) at RT. Ammonia gas was bubbled through THF (355 mL) at 0° C. for 20 min. Neat cyclopropylsulfonyl chloride (1a, 15 g, 0.11 mol) was dropwise added to the solution. The resulting solution was allowed to warm to room temperature and stirred for 17 h. The resulting suspension was filtered through a plug of silica gel, eluting with ethyl acetate. The filtrate was concentrated in vacuo to afford 11.5 g (89percent) of cyclopropylsulfonamide 1b. [00279] Ammonia gas was bubbled through a gas dispersion tube into THF (40 mL) cooled to 0 Example 46 Cyclopropylsulfonyl chloride (1.4g, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at rt. The reaction was stirred at rt for 72 h. The precipitate was filtered and discarded. The clear filtrate was evaporated in vacuo and the white residue was dried on vacuum for 24 h to give cyclopropylsulfonamide (0.88 g, 74percent).Cyclopropylsulfonyl chloride (1.4g, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at rt. The reaction was stirred at rt for 72 h. The precipitate was filtered and discarded. The clear filtrate was evaporated in vacuo and the white residue was dried on vacuum for 24 h to give cyclopropylsulfonamide (0.88 g, 74percent).Cyclopropylsulfonyl chloride (1.4 g, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at RT. The reaction was kept at RT for 3 days. The large amount of precipitation was filtered and discarded. The clear filtrate was evaporated in vacuo and the white residue was dried on vacuum for 24 hours to give the cyclopropylsulfonamide (0.88 g, 74percent). Cyclopropylsulfonyl chloride (IAg, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at RT. The reaction was kept at RT for 3 days. The large amount of precipitation was filtered and discarded. The clear filtrate was evaporated in vacuo and the white residue was dried on vacuum for 24 hours to give the cyclopropylsulfonamide (0.88 g, 74percent). Step 3A: Cyclopropylsulfonyl chloride (1.4g, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at RT. The reaction was kept at RT for 3 days. The large amount of precipitation was filtered and discarded. The clear filtrate was General procedure: Standard Procedure D for the Preparation of Sulfonamides (0054) A solution of sulfonyl chloride in methanol and ammonium hydroxide solution was stirred at 0° C. or room temperature. After the reaction was complete, methanol was removed under reduced pressure. The solution was extracted with ethyl acetate. The combined organic layers were dried over MgSOCyclopropanesulfonamide Cyclopropanesulfonamide A mixture of 50 ml of 25percent aqueous ammonia solution and 50 ml of THF was initially charged, and then 10.00 g of cyclopropanesulfonyl chloride in 10 ml of THF were slowly added dropwise and the mixture was stirred for 16 hours. After concentration by rotary evaporation and coevaporation with toluene, the residue was extracted by stirring with 100 ml of ethyl acetate and the solids were filtered off. The organic phase was dried over NaStep B: A yield of >95percent was routinely obtained of cyclopropylsulfonamide following the same TFA deprotection procedure used above (Method B) for the deprotection of cyclopropanesulfonic acid tert-butylamide except that of cyclopropylsulfonylamine tert-butyl carbamate was used in place of N-tert-butyl-(1-methyl)cyclopropyl-sulfonamide.Preparation of Sulfonyl Compounds

Molecular Weight:121.16
XLogP3:-0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:121.01974964
Monoisotopic Mass:121.01974964
Topological Polar Surface Area:68.5
Heavy Atom Count:7
Complexity:150
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes