ethenesulfonyl chloride

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

Procedure: This compound was prepared, in an analogous manner as described in Example 1, from (S)-4-(8-amino-3-(piperidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide (intermediate 25) and ethenesulfonyl chloride prepared according to procedures described by King et. al. in Can. J. Chem. 66 (1988) pp 1109-1116, to afford the title compound (6.1 mg, 20.5%). Data: UPLC(B) Rt: 1.24 min; m/z 572.2 (M+H)+. This compound was prepared, in an analogous manner prepared

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

Procedure: Ethensulfonic acid {2-[4-(4-chloro-3-methoxy-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-2-methyl-propyl}-amide A solution of ethenesulfonyl chloride (J. Marchand-Brynaert et al., Tetrahedron 1966, 52, 5591) (230 mg, 1.8 mmol) in dichloromethane (10 ml) was cooled to −78° C. and treated with a solution of the product of Example 2 and triethylamine (0.4 ml, 3 mmol) in dichloromethane (10 ml). 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 (254 mg, 38%); MS(ES+) m/e 447/449 [M+H]+. Step 2. 2-(4-Methyl-piperazin-1-yl)-ethanesulfonic acid {2-[4-(4-chloro-3-methoxy-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-2-methyl-propyl}-amide A solution of the produce of Step 1 (110 mg, 0.25 mmol) and N-methylpiperazine (50 mg, 0.5 mmol) in dichloromethane (5 ml) was stirred at room temperature for 72 hours. The solvent was evaporated and the residue was purified by silica gel chromatography to give the title compound (98 mg, 72%); MS(ES+) m/e 547/549 [M+H]+. Step 3. 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 The title compound was prepared from the product of Step 2 using the method described in Example 3 and the product purified by silica gel chromatography; MS(ES+) m/e 533/535 [M+H]+. 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 the solvent evaporated

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

Procedure: 15 ml of water was added to 9.6 g of 1-naphthalene sulfinic acid and a solution of 2 g of sodium hydroxide in 5 ml of water was added to the mixture. To the solution there was added a solution of 6.3 g of vinylsulfonyl chloride in 20 ml of acetronitrile at room temperature with stirring and the mixture was stirred at room temperature for additional 24 hours. The reaction solution was poured into 300 ml of water, the resulting precipitates were recovered through filtration and recrystallized from a mixed solvent of benzene and ethanol to give 3.5 g of vinyl-1-naphthyldisulfone. the mixture was stirred at room temperature for additional 24 hours the resulting precipitates were recovered through filtration recrystallized from a mixed solvent of benzene and ethanol

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

Procedure: 130 ml of tetrahydrofuran was added to a mixture of 7.6 g of N-benzoyl-N-methylhydroxylamine and 6.3 g of vinylsulfonyl chloride and a solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added to the mixture over 2 hours with stirring while cooling the mixture so that the temperature was maintained at 25° C. or less. The reaction was continued for additional 2 hours at a temperature ranging from 15° to 25° C. and then the same procedures used in Preparation Example 4 were repeated to give 9.2 g of o-vinylsulfonyl-N-benzoyl-N-methylhydroxylamine. while cooling the mixture so that the temperature was maintained at 25° C. or less ranging from 15° to 25° C. the same procedures used in Preparation Example 4

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

Procedure: 15 ml of water was added to 9.6 g of 1-naphthalene sulfinic acid and a solution of 2 g of sodium hydroxide in 5 ml of water was added to the mixture. To the solution there was added a solution of 6.3 g of vinylsulfonyl chloride in 20 ml of acetonitrile at room temperature with stirring and the mixture was stirred at room temperature for additional 24 hours. The reaction solution was poured into 300 ml of water, the resulting precipitates were recovered through filtration and recrystallized from a mixed solvent of benzene and ethanol to give 3.5 g of vinyl-1-naphthyldisulfone. the mixture was stirred at room temperature for additional 24 hours the resulting precipitates were recovered through filtration recrystallized from a mixed solvent of benzene and ethanol

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

Procedure: 130 ml of tetrahydrofuran was added to a mixture of 7.6 g of N-benzoyl-N-methylhydroxylamine and 6.3 g of vinylsulfonyl chloride and a solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added to the mixture over 2 hours with stirring while cooling the mixture so that the temperature was maintained at 25 ° C. or less. The reaction was continued for additional 2 hours at a temperature ranging from 15° to 25 ° C. and then the same procedures used in Preparation Example 4 were repeated to give 9.2 g of o-vinylsulfonyl-N-benzoyl-N-methylhydroxylamine. while cooling the mixture so that the temperature was maintained at 25 ° C. or less ranging from 15° to 25 ° C. the same procedures used in Preparation Example 4

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

Procedure: 15 ml of water was added to 9.6 g of 1-naphthalene sulfinic acid and a solution of 2 g of sodium hydroxide in 5 ml of water was added to the mixture. To the solution there was added a solution of 6.3 g of vinylsulfonyl chloride in 20 ml of acetonitrile at room temperature with stirring and the mixture was stirred at room temperature for additional 24 hours. The reaction solution was poured into 300 ml of water, the resulting precipitates were recovered through filtration and recrystallized from a mixed solvent of benzene and ethanol to give 3.5 g of vinyl-1-naphthyldisulfone. the mixture was stirred at room temperature for additional 24 hours the resulting precipitates were recovered through filtration recrystallized from a mixed solvent of benzene and ethanol

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

Procedure: 130 ml of tetrahydrofuran was added to a mixture of 7.6 g of N-benzoyl-N-methylhydroxylamine and 6.3 g of vinylsulfonyl chloride and a solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added to the mixture over 2 hours with stirring while cooling the mixture so that the temperature was maintained at 25° C. or less. The reaction was continued for additional 2 hours at a temperature ranging from 15° to 25° C. and then the same procedures used in Preparation Example 4 were repeated to give 9.2 g of o-vinylsulfonyl N-benzoyl-N-methylhydroxylamine. while cooling the mixture so that the temperature was maintained at 25° C. or less ranging from 15° to 25° C. the same procedures used in Preparation Example 4

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

Procedure: 15 ml of water was added to 9.6 g of 1-naphthalene sulfinic acid and a solution of 2 g of sodium hydroxide in 5 ml of water was added to the mixture. To the solution there was added a solution of 6.3 g of vinylsulfonyl chloride in 20 ml of acetonitrile at room temperature with stirring and the mixture was stirred at room temperature for additional 24 hours. The reaction solution was poured into 300 ml of water, the resulting precipitates were recovered through filtration and recrystallized from a mixed solvent of benzene and ethanol to give 3.5 g of vinyl-1-naphthyldisulfone. the mixture was stirred at room temperature for additional 24 hours the resulting precipitates were recovered through filtration recrystallized from a mixed solvent of benzene and ethanol

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

Procedure: 130 ml of tetrahydrofuran was added to a mixture of 7.6 g of N-benzoyl-N-methylhydroxylamine and 6.3 g of vinylsulfonyl chloride and a solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added to the mixture over 2 hours with stirring while cooling the mixture so that the temperature was maintained at 25° C. or less. The reaction was continued for additional 2 hours at a temperature ranging from 15° to 25° C. and then the same procedures used in Preparation Example 4 were repeated to give 9.2 g of o-vinylsulfonyl-N-benzoyl-N-methylhydroxylamine. while cooling the mixture so that the temperature was maintained at 25° C. or less ranging from 15° to 25° C. the same procedures used in Preparation Example 4

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

Procedure: 15 ml of water was added to 9.6 g of 1-naphthalene sulfinic acid and a solution of 2 g of sodium hydroxide in 5 ml of water was added to the mixture. To the solution there was added a solution of 6.3 g of vinylsulfonyl chloride in 20 ml of acetonitrile at room temperature with stirring and the mixture was stirred at room temperature for additional 24 hours. The reaction solution was poured into 300 ml of water, the resulting precipitates were recovered through filtration and recrystallized from a mixed solvent of benzene and ethanol to give 3.5 g of vinyl-1-naphthyldisulfone. the mixture was stirred at room temperature for additional 24 hours the resulting precipitates were recovered through filtration recrystallized from a mixed solvent of benzene and ethanol

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

Procedure: 130 ml of tetrahydrofuran was added to a mixture of 7.6 g of N-benzoyl-N-methylhydroxylamine and 6.3 g of vinylsulfonyl chloride and a solution of 5.1 g of triethylamine in 20 ml of tetrahydrofuran was dropwise added to the mixture over 2 hours with stirring while cooling the mixture so that the temperature was maintained at 25° C. or less. The reaction was continued for additional 2 hours at a temperature ranging from 15° to 25° C. and then the same procedures used in Preparation Example 4 were repeated to give 9.2 g of o-vinylsulfonyl-N-benzoyl-N-methylhydroxylamine. while cooling the mixture so that the temperature was maintained at 25° C. or less ranging from 15° to 25° C. the same procedures used in Preparation Example 4