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Structure of 6608-47-5 * Storage: {[proInfo.prStorage]}
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With 2,6-dimethylpyridine In diethyl ether at -60 - 25℃; for 0.75 h;
Stirrer,thermometer,Into a three-necked flask having an internal volume of 300 mL equipped with a dropping funnel,25.7 g (0.158 mol) of 2-chloroethanesulfonyl chloride,150 mL of diethyl ether was charged,And cooled to -60 ° C. with stirring.To the dropping funnel, 2,6-lutidine20.2 g (0.189 mol)And 30 mL of diethyl ether, and the mixture was added dropwise at an internal temperature of -61 ° C. over 5 minutes.After completion of the dropwise addition, the reaction mixture was stirred at an internal temperature of -60 ° C. for 5 minutes,The temperature was raised to 25 ° C. and stirred for 45 minutes.Then, the inner temperature was cooled to 5 ° C., and 20 mL of a 1percent sulfuric acid aqueous solution was added. Subsequently, the organic layer obtained by separation was washed with 20 mL of water, and then the organic layer was washed with 20percent aqueous sodium chloride solution. Sodium sulfate was added to the obtained organic layer, followed by drying and filtration. The filtrate was concentrated under reduced pressure to obtain 19 g of a black oil. This oil was subjected to simple distillation under conditions of 13.3 Pa at 45 ° C. to obtain 14.35 g (purity: 97.3percent, 0.11 mol) of vinyl chlorosulfone having the following structure (yield: 69.6percent).
63%
Stage #1: With 2,6-dimethylpyridine In diethyl ether at -60 - 20℃; Stage #2: With sulfuric acid In diethyl ether; water at 0℃;
Ethenesulfonyl chloride. A stirred solution of 2-chloroethanesulfonyl chloride (50 g, 0.307 mol) in dry ether (400 ML) was treated at-60 °C to-50 °C under an atmosphere of nitrogen with a solution of 2,6-lutidine (42.2 mL, 0.36 mol) in dry ether (60 mL) and then with a further portion of dry ether (200 mL). The stirred reaction mixture was allowed to warm to room temperature, cooled to 0 °C and then treated slowly with dilute aqueous sulfuric acid (1percent; 125 mL). The ethereal phase was separated, washed with dilute aqueous sulfuric acid (1 percent ; 125 mL) and brine (2 X 120 mL), dried over magnesium sulfate, and concentrated under reduced pressure (500 mm Hg) to give a crude oil that was purified by distillation to give ethenesulfonyl chloride (C. S. Rondestveldt, J. Amer. Chem. Soc., 76, 1954, 1926) (24.6 g, 63percent), b. p. 27. 2°C/0.2 mm Hg. 1H-NMR (CDCl3) δ 7.20 (dd, J = 16.2 and 9.4 Hz, 1H), 6.55 (dd, J= 16.2 and 1.7 Hz, 1H), and 6.24 (dd, J= 9.4 and 1.7 Hz, 1H).
Reference:
[1] Organic Letters, 2010, vol. 12, # 2, p. 364 - 366
[2] Patent: JP5840146, 2016, B2, . Location in patent: Paragraph 0094; 0095
[3] Patent: WO2004/48350, 2004, A2, . Location in patent: Page 64-65
[4] Journal of Labelled Compounds and Radiopharmaceuticals, 2018, vol. 61, # 11, p. 847 - 856
[5] Journal of the American Chemical Society, 1954, vol. 76, p. 1926,1928
[6] Canadian Journal of Chemistry, 1984, vol. 62, # 10, p. 1977 - 1995
[7] Journal of the American Chemical Society, 1982, vol. 104, p. 7108
[8] Tetrahedron, 1996, vol. 52, # 15, p. 5591 - 5606
[9] Patent: US2007/232668, 2007, A1, . Location in patent: Page/Page column 22
[10] Patent: WO2009/11851, 2009, A1, . Location in patent: Page/Page column 452; 467
[11] Patent: US2009/130057, 2009, A1, . Location in patent: Page/Page column 56
[12] Tetrahedron Letters, 2011, vol. 52, # 45, p. 5934 - 5939
[13] Journal of the American Chemical Society, 2013, vol. 135, # 47, p. 17869 - 17880
[14] European Journal of Organic Chemistry, 2014, vol. 2014, # 15, p. 3210 - 3224
[15] Chemistry - A European Journal, 2015, vol. 21, # 18, p. 6906 - 6912
[16] Patent: WO2017/84630, 2017, A1, . Location in patent: Paragraph 00787
2
[ 31469-08-6 ]
[ 6608-47-5 ]
Yield
Reaction Conditions
Operation in experiment
92%
With triethylamine In dichloromethane at 20℃;
General procedure: 1 mmol compound 2 was dissolve in 10~20 mL DCM. 2 equiv TEA was added dropwise at room temperature. Stirred for several minutes, the reaction mixture was washed with brine (5~10 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated to yield faintly yellow or colorless oil product with 85-95percent yield.
With phosphorus pentachloride; triethylamine In toluene
SYNTHESIS EXAMPLE 4 12.7 g (0.1 mole) of vinylsulfonyl chloride prepared from sodium vinylsulfonate and phosphorus pentachloride was added to 200 ml of toluene, and 18.4 g (0.1 mole) of p-aminodiphenylamine and 10 g of triethylamine were gradually added to the solution. The mixture was stirred at 0° C. for 2 hours. The resulting precipitate was separated to afford 22.2 g (yield 81percent) of N-(4-anilino)phenylvinylsulfonamide having a melting point of 126° C.
Reference:
[1] Patent: US4298522, 1981, A,
4
[ 3039-83-6 ]
[ 6608-47-5 ]
Reference:
[1] Journal of Organic Chemistry, 1968, vol. 33, p. 4343 - 4346
5
[ 15805-34-2 ]
[ 6608-47-5 ]
Reference:
[1] Patent: US2772307, 1953, ,
6
[ 75-84-3 ]
[ 31469-08-6 ]
[ 6608-47-5 ]
Reference:
[1] Canadian Journal of Chemistry, 1988, vol. 66, p. 1109 - 1116
With hydrogen fluoride; Methyl benzenesulfonate; at 100℃; for 6h;Autoclave;
506.2 g of <strong>[6608-47-5]vinylsulfonyl chloride</strong> was added to a 1000 mL autoclave.Turn on the agitation. Inject 25 g of methyl benzenesulfonate as a catalyst,120 g of liquid hydrogen fluoride was charged, and the kettle was heated to 100 C.Maintain the reaction temperature at 100 ± 5 C, react for 6 hours, release pressure, wash with water,After separation, the organic phase is distilled under reduced pressure.Collecting fractions of 53-54 C / 70 mm Hg,Obtained 336.4g of product,The content was 98.2%, and the yield was 75.0%.
With tetrachloromethane; at 20℃; for 5h;Irradiation;
1,2-Dichloroethanesulfonyl chloride. A stirred solution of chlorine in a solution of <strong>[6608-47-5]ethenesulfonyl chloride</strong> (32 g, 0.25 mol) in carbon tetrachloride was irradiated at about room temperature (200W light) for 5 h. The reaction mixture was concentrated under reduced pressure (50 mm Hg) and the involatile residue was fractionally distilled to give 1,2-dichloroethanesulfonyl chloride (Goldstein et al. Zh. Obshch. Khim., 28, 1958, 2107) (15,5 g, 31%), b. p. 75 C/0. 7 mm Hg. 1H-NMR (CDCl3) delta 5.29 (dd, J = 8.9 and 3.3 Hz, 1H), 4.40 (dd, J = 12.4 and 3.3 Hz, 1H), and 3.97 (dd, J = 12.4 and 8.9 Hz, 1H).
With 2,6-dimethylpyridine; In diethyl ether; at -60 - 25℃; for 0.75h;
Stirrer,thermometer,Into a three-necked flask having an internal volume of 300 mL equipped with a dropping funnel,25.7 g (0.158 mol) of 2-chloroethanesulfonyl chloride,150 mL of diethyl ether was charged,And cooled to -60 C. with stirring.To the dropping funnel, 2,6-lutidine20.2 g (0.189 mol)And 30 mL of diethyl ether, and the mixture was added dropwise at an internal temperature of -61 C. over 5 minutes.After completion of the dropwise addition, the reaction mixture was stirred at an internal temperature of -60 C. for 5 minutes,The temperature was raised to 25 C. and stirred for 45 minutes.Then, the inner temperature was cooled to 5 C., and 20 mL of a 1% sulfuric acid aqueous solution was added. Subsequently, the organic layer obtained by separation was washed with 20 mL of water, and then the organic layer was washed with 20% aqueous sodium chloride solution. Sodium sulfate was added to the obtained organic layer, followed by drying and filtration. The filtrate was concentrated under reduced pressure to obtain 19 g of a black oil. This oil was subjected to simple distillation under conditions of 13.3 Pa at 45 C. to obtain 14.35 g (purity: 97.3%, 0.11 mol) of vinyl chlorosulfone having the following structure (yield: 69.6%).
63%
Ethenesulfonyl chloride. A stirred solution of 2-chloroethanesulfonyl chloride (50 g, 0.307 mol) in dry ether (400 ML) was treated at-60 C to-50 C under an atmosphere of nitrogen with a solution of 2,6-lutidine (42.2 mL, 0.36 mol) in dry ether (60 mL) and then with a further portion of dry ether (200 mL). The stirred reaction mixture was allowed to warm to room temperature, cooled to 0 C and then treated slowly with dilute aqueous sulfuric acid (1%; 125 mL). The ethereal phase was separated, washed with dilute aqueous sulfuric acid (1 % ; 125 mL) and brine (2 X 120 mL), dried over magnesium sulfate, and concentrated under reduced pressure (500 mm Hg) to give a crude oil that was purified by distillation to give ethenesulfonyl chloride (C. S. Rondestveldt, J. Amer. Chem. Soc., 76, 1954, 1926) (24.6 g, 63%), b. p. 27. 2C/0.2 mm Hg. 1H-NMR (CDCl3) delta 7.20 (dd, J = 16.2 and 9.4 Hz, 1H), 6.55 (dd, J= 16.2 and 1.7 Hz, 1H), and 6.24 (dd, J= 9.4 and 1.7 Hz, 1H).
With triethylamine; In dichloromethane; at -78 - 0℃; for 1.25h;
2-Chloroethanesulfonyl chloride (5.7 mmol, 930 mg) was dissolved in dichloromethane (10 mL). Obtained solution was cooled down to -78 C. Triethylamine (TEA), (5.7 mmol, 0.8 mL) was added, and the reaction mixture was stirred at -78 C. for 30 min, then for 45 min at 0 C. The reaction mixture was cooled to -78 C. and the mixture of (S)-methylbenzylamine (5.7 mmol, 690 mg) and TEA (5.7 mmol, 0.8 mL) in dichloromethane (10 mL) was added. Stirring at -78 C. was continued for additional 20 min, then cooling bath was removed and the reaction mixture was stirred for 20 min at rt. Solvents were evaporated to dryness, and crude product was purified by LC chromatography (ISCO LC purification system) using hexanes:ethyl acetate gradient up to 50% ethyl acetate as eluent, to give 0.78 g of sulfonamide (A) (yield 65%).
With triethylamine; In dichloromethane; at -78 - 20℃; for 2.16667h;
Scheme 1; Methods B and C; Choroethylsulfonyl chloride (3.4 g, 0.02 mol) was dissolved in dichloromethane (100 ml_) and cooled to -780C under nitrogen. Triethylamine (2.12 g, 1 eq) was added and the reaction was stirred at -780C for 10 minutes. The reaction mixture was warmed to room temperature and stirred for 2 hours. Bis-4-methoxydibenzyl- amine.HCI (6 g, 0.02 mol) was added, followed by triethylamine (4.24 g, 2 eq) and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane (100 ml_) and washed with 10% HCI and brine. The solvent was removed in vacuo and the product was isolated by silica gel chromatography using a gradient of 0-50% ethyl acetate/hexane mixture as eluent to afford 1.37 g of compound 2. 1H-NMR (CDCI3 400 MHz) delta 7.25 (d, 4H), 6.87 (d, 4H), 6.26 (m, 2H), 5.86 (d, 1 H), 4.19 (s, 4H)1 3.81 (s, 6H).
With triethylamine; In diethyl ether; at -24 - 20℃; for 2h;CCl4-dry ice bath;
A solution of TEA (7.67 mL, 55.0 mmol) in Et2O (50 ml) was added to a solution of 2-chloroethanesulfonyl chloride (5.22 mL, 50 mmol) in Et2O (100 ml) at -24 C. (CCl4-dry ice bath) and the mixture was stirred and allowed to warm to rt over 2 h. The reaction mixture was filtered to remove a white precipitate and the filtrate was concentrated (20 mL of volume). NH3 was bubbled into the solution of ethenesulfonyl chloride (1.266 g, 10.00 mmol) in Et2O (20 mL) for 10 min and the white precipitate was removed by filtration. The filtrate was concentrated to yield ethenesulfonamide (180 mg, 1.680 mmol, 16.80% yield) as a colorless gel which was used without further purification. 1H NMR (300 MHz, CD3OD) delta ppm 6.80 (dd, J=16.5, 9.9 Hz, 1H), 6.16 (d, J=16.5 Hz, 1H), 5.87 (dd, J=9.9 Hz, 1H). LC-MS retention time 0.17 min; m/z 108 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10 u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.
With pyridine; In dichloromethane; at -78℃; for 0.333333h;
To a solution of 2-chioroethanesulfonyl chloride (0.64 mL, 6.1 mmol) inDCM (10 mL) was added pyridine (0.97 g, 12.2 mmol) at -78C and the resulting mixture wasstirred at the same temperature for 20 mm. The reaction was warmed to room temperature while stirring and stirred for another 20 mm at the same temperature.
With triethylamine; In tetrahydrofuran; water; at 0℃; for 1h;
Example 7 (Tablel, entty 3, and Scheme 6): Preparation of 2-[2-(aminocarbonyl)(2- bromoethyl)-4,6-dinitroanilino] ethyl ethylenesulfonate (14); A solution of 2-[(2- brofnoethyl)(2-hydroxyethyl)amino]-3,5-dinitrobenzamide (12b) (754 mg, 2.0 mmol) in dry THF (100 mL) was cooled in an ice-bath at 0 0C and then treated with Et3N (0.7 mL), followed by <strong>[6608-47-5]vinylsulfonyl chloride</strong> (316 mg, 2.5 mmol) dropwise. After stirring for 30 min. at 0 0C, ice-water was added, and after a further 30 min the aqueous phase was extracted with CH2Cl2 (2x50 mL). The combined organic phases were dried, concentrated under reduced pressure and filtered through a short column, eluting with EtOAc/petroleum ether (2:1), to give 2-[2-(aniinocarbonyl)(2-bro?ioethyl)-4,6-dinitroanilino]ethyl ethylenesulfonate (14) (864 mg, 93%) as a yellow solid: mp (EtOAc/petroleum ether) 117-119 0C; 1H NMR [(CD3)2SO] delta 8.73 (dj = 2.8 Hz, 1 H), 8.33 (dj = 2.8 Hz, 1 H), 8.18 (s, 1 H), 7.96 (s, 1 H), 6.89 (qj = 10.1 Hz, 1 H), 6.31 (d, / = 9.6 Hz, 1 H), 6.28 (d, / = 2.8 Hz, 2 H), 4.20 (t, / = 5.4 Hz, 2 H), 3.55 (m, 2 H), 3.49 (m, 4 H), 167.1, 145.7, 145.6, 141.1, 136.3, 132.1, 131.5, 127.2, 122.1, 68.2, 54.6, 51.2, 29.7. Anal. Calcd. for C13H15BrN4O8S: C, 33.4; H, 3.2, N, 12.0. Found: C, 33.7; H, 3.3; N, 11.9%.
Ethenesulfonic acid {2-[4-(4-chloro-3-methoxy-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-2-methyl-propyl}-amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
38%
With triethylamine; In dichloromethane; at -78℃; for 1h;
Example 42: 2-(4-Methyl-piperazin-1-yl)-ethanesulfonic acid {2-[4-(4-chloro-3-hydroxy-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-2-methyl-propyl}-amide; Step 1. Ethenesulfonic acid {2-[4-(4-chloro-3-methoxy-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-2-methyl-propyl}-amide A solution of <strong>[6608-47-5]ethenesulfonyl chloride</strong> (J. Marchand-Brynaert et al., Tetrahedron 1996, 52, 5591) (230mg, 1.8mmol) in dichloromethane (10ml) was cooled to -78C and treated with a solution of the product of Example 2 and triethylamine (0.41ml, 3mmol) in dichloromethane (10ml). After 1 hour the reaction mixture was warmed to room temperature and the solution washed with saturated sodium hydrogen carbonate solution. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate, filtered and the solvent evaporated to give the title compound (254mg, 38%); MS(ES+) m/e 447/449 [M+H]+.
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;
Intermediate E (0.44 g, 1 mmol) and diisopropylethylamine (0.26 mL, 1.5 mmol) were dissolved in dichloromethane. 2-Chloroethanesulfonyl chloride (0.24 g, 1.5 mmol) was added to the solution, which was stirred at room temperature overnight. The organic layer was washed with a 10% citric acid solution then saturated aqueous NaHCO3, dried over MgS04 and filtered. The solvent was removed in vacuo and the crude material purified by column chromatography eluting with ethyl acetate/heptane (3/2) to give 0. 38 g (72%) of F as a colorless oil.
To [4-AMINO-2- (PIPERIDIN-4-YLAMINO)-THIAZOL-5-YL]- (2, 6-DIFLUORO-PHENYL)-METHANONE (2. 00 g, 5. 92 mmol ; Example A6) and triethylamine (1. 65 ML, 11. 8 MMOL) in anhydrous'THF (100 ML) stirred at 0 C, was added dropwise a solution of <strong>[6608-47-5]ethenesulfonyl chloride</strong> (0. 969 g, 7. 70 MMOL, see Rondestvedt, et AL., J. Amer. Chem. Soc., 76, 1926-1929 (1954)) in THF (20 ML). The yellow suspension stirred at 0 C for 10 min, acidified to pH 3 with 1N HCI, and the solvent removed. The resultant residue was dissolved in MEOH (5 ml), cooled with ice-water bath, and diluted with 1N HCl (100 ml). After stirring rapidly for 20 min., a white solid was filtered off, washed with water, and dried under vacuum. Column chromatography with 2. 5% MEOH in CHC13 provided 2. 15 g of white solid in 85% yield, which was used without any further purification. 'H NMR (DMSO-d6) : 8 8. 84 (bs, 1H), 8. 07 (bs, 2H), 7. 50 (m, 1H), 7. 17 (dd, 2H, J=7. 7, 8. 0 Hz), 6. 79 (dd, 1H, J=10. 1, 16. 6 Hz), 6. 14 (d, 1H, J=10. 1 Hz), 6. 10 (d, 1H, J=16. 6 Hz), 3. 05 (m, 1H), 2. 79 (t, 2H, J=10. 6 Hz). ESMS (M+H+) : 429.
With phosphorus pentachloride; triethylamine; In toluene;
SYNTHESIS EXAMPLE 4 12.7 g (0.1 mole) of vinylsulfonyl chloride prepared from sodium vinylsulfonate and phosphorus pentachloride was added to 200 ml of toluene, and 18.4 g (0.1 mole) of p-aminodiphenylamine and 10 g of triethylamine were gradually added to the solution. The mixture was stirred at 0 C. for 2 hours. The resulting precipitate was separated to afford 22.2 g (yield 81%) of N-(4-anilino)phenylvinylsulfonamide having a melting point of 126 C.
5-bromo-3-[1-(ethenylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With triethylamine; In dichloromethane; at 20℃; for 0.5h;
To a solution of 5-bromo-3-(4-piperidinyl)-1 H-indole-7-carboxamide (500 mg, 1.3 mmol) in methylene chloride at room temperature, triethylamine (0.44 mL, 3.2 mmol) and 2- chloroethylsulfonyl chloride (0.168 mL, 1 .6 mmol) were added. The reaction mixture was stirred for 30 min. Removed the solvent, the residue was purified by combiflash to give the title compound (150 mg, 75%). LCMS m/z 413.8 (M+H), 1.96 min
With triethylamine; In dichloromethane; at 0℃; for 0.5h;
To a solution of 5-phenyl-3-(4-piperidinyl)-1 H-indole-7-carboxamide (260 mg, 0.8 mmol) in CH2CI2 at O0C, triethylamine (0.44 ml_, 3.2 mmol) and 2-chloroethylsulfonyl chloride (0.168 m._, 1.6 mmol) were added. The reaction mixture was stirred at O0C for 30 min. The reaction mixture was partitioned between CH2CI2 (100 ml_) and water (50 ml_). The organic layer was separated and the aqueous layer was extracted with CH2CI2 (2x100 ml_). The combined organic phase was washed with brine (50 mL), dried over magnesium sulfate and filtered. The solvent was removed under reduced pressure and purified via filtration through an SPE Cartridge (Aminopropyl NH2, 500 mg/6 mL) to give the title compound (245 mg, 75%). LCMS m/z 410 (MH-H).
With triethylamine; In dichloromethane; at -78 - 20℃; for 0.666667h;
2-Chloroethanesulfonyl chloride (5.7 mmol, 930 mg) was dissolved in dichloromethane (10 mL). Obtained solution was cooled down to -78 C. Triethylamine (TEA), (5.7 mmol, 0.8 mL) was added, and the reaction mixture was stirred at -78 C. for 30 min, then for 45 min at 0 C. The reaction mixture was cooled to -78 C. and the mixture of (S)-methylbenzylamine (5.7 mmol, 690 mg) and TEA (5.7 mmol, 0.8 mL) in dichloromethane (10 mL) was added. Stirring at -78 C. was continued for additional 20 min, then cooling bath was removed and the reaction mixture was stirred for 20 min at rt. Solvents were evaporated to dryness, and crude product was purified by LC chromatography (ISCO LC purification system) using hexanes:ethyl acetate gradient up to 50% ethyl acetate as eluent, to give 0.78 g of sulfonamide (A) (yield 65%).
With triethylamine; In dichloromethane; at 20℃; for 2h;
Scheme 1; Methods B and C; Choroethylsulfonyl chloride (3.4 g, 0.02 mol) was dissolved in dichloromethane (100 ml_) and cooled to -780C under nitrogen. Triethylamine (2.12 g, 1 eq) was added and the reaction was stirred at -780C for 10 minutes. The reaction mixture was warmed to room temperature and stirred for 2 hours. Bis-4-methoxydibenzyl- amine.HCI (6 g, 0.02 mol) was added, followed by triethylamine (4.24 g, 2 eq) and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane (100 ml_) and washed with 10% HCI and brine. The solvent was removed in vacuo and the product was isolated by silica gel chromatography using a gradient of 0-50% ethyl acetate/hexane mixture as eluent to afford 1.37 g of compound 2. 1H-NMR (CDCI3 400 MHz) delta 7.25 (d, 4H), 6.87 (d, 4H), 6.26 (m, 2H), 5.86 (d, 1 H), 4.19 (s, 4H)1 3.81 (s, 6H).
With triethylamine; In tetrahydrofuran; at 0℃; for 1.16667h;
Example M26: 1-Methylcyclopropyl 4-((5-(4-(vinylsulfonyl)piperazin-l- yl)pyrazin-2-yloxy)methyl)piperidine-l-carboxylate.[00246] A solution of MIc (308 mg, 0.82 mmol) in tetrahydorfuran (4 mL) is cooled in an ice/water bath and treated with triethylamine (299 mg, 3.0 mmol) followed by 2-chloroethanesulfonyl chloride (401 mg, 2.5 mmol) added over 10 minutes. The reaction is stirred for an hour and then evaporated and partitioned between water and ethyl acetate. The organics are exracted with water twice more, dried over MgSO4, filtered evaporated and purified by silica gel using a linear gradient of 0-100% ethyl acetate in hexane to afford M26; 1H NMR (400 MHz, CD3CN) delta 7.91 (d, J = 2.9Hz, IH), 7.15 (dd, J = 9.1, 3.1 Hz, IH), 6.65 (d, J = 9.1 Hz, IH), 4.19 (m, 2H), 3.81 (d, J = 6.3 Hz, 2H), 3.54 (m, 4H), 3.34 (m, 4H), 3.08 (ddd, J = 13.1, 2.8, 2.8 Hz, 2H), 2.80 (s, 3H), 2.04 (m, IH), 1.92 (m, 2H), 1.44 (m, 2H), 1.28 (m, 6H); ESIMS m/z for (M+H)+ C2]H32N5O5S calcd: 466.2, found: 466.2.