1-(PROPANE-2-SULFONYL)-PIPERAZINE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(Propane-2-sulfonyl)-piperazine (0.0286 mmol) was dissolved in 0.25 mL of methylene chloride and added to a solution of 4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (0.024 mmol, example 3) and diisopropylethylamine (0.072 mmol) in. 25 mL of methylene chloride in a 4 mL vial. The vial was capped and shaken overnight at room temperature. The reaction mixture was diluted with 1 mL of methylene chloride and 1 mL of water. The vial was agitated and centrifuged. The organic layer was transferred to a 4 mL vial and concentrated in vacuo to give [4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(propane-2-sulfonyl)-piperazin-1-yl]-methanone. LR-MS (M+H)+=697.4. The vial was capped The vial was agitated concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-BOC-piperazine (0.617 mmol) and diisopropylethylamine (0.679 mmol) in 0.5 mL of methylene chloride was added to a 4 mL vial. Propane-2-sulfonyl chloride (0.679 mmol) was added to the vial, and the reaction mixture was shaken overnight at room temperature. When the reaction was complete, it was diluted with 1.5 mL of methylene chloride and extracted with 1 mL of 1N solution of hydrogen chloride followed by 1 mL of 10% potassium carbonate solution. The organic layer was concentrated in vacuo. The residue was dissolved in 0.5 mL of tetrahydrofuran and 4M solution of hydrogen chloride in dioxane (0.5 mL). The solution was shaken overnight at room temperature then concentrated in vacuo to give 1-(propane-2-sulfonyl)-piperazine. extracted with 1 mL of 1N solution of hydrogen chloride The organic layer was concentrated in vacuo The residue was dissolved in 0.5 mL of tetrahydrofuran The solution was shaken overnight at room temperature then concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(Propane-2-sulfonyl)-piperazine (0.0286 mmol) was dissolved in 0.25 mL of methylene chloride and added to a solution of 4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (0.024 mmol, example 3) and diisopropylethylamine (0.072 mmol) in. 25 mL of methylene chloride in a 4 mL vial. The vial was capped and shaken overnight at room temperature. The reaction mixture was diluted with 1 mL of methylene chloride and 1 mL of water. The vial was agitated and centrifuged. The organic layer was transferred to a 4 mL vial and concentrated in vacuo to give [4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(propane-2-sulfonyl)-piperazin-1-yl]-methanone. LR-MS (M+H)+=697.4. The vial was capped The vial was agitated concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-BOC-piperazine (0.617 mmol) and diisopropylethylamine (0.679 mmol) in 0.5 mL of methylene chloride was added to a 4 mL vial. Propane-2-sulfonyl chloride (0.679 mmol) was added to the vial, and the reaction mixture was shaken overnight at room temperature. When the reaction was complete, it was diluted with 1.5 mL of methylene chloride and extracted with 1 mL of 1N solution of hydrogen chloride followed by 1 mL of 10% potassium carbonate solution. The organic layer was concentrated in vacuo. The residue was dissolved in 0.5 mL of tetrahydrofuran and 4M solution of hydrogen chloride in dioxane (0.5 mL). The solution was shaken overnight at room temperature then concentrated in vacuo to give 1-(propane-2-sulfonyl)-piperazine. extracted with 1 mL of 1N solution of hydrogen chloride The organic layer was concentrated in vacuo The residue was dissolved in 0.5 mL of tetrahydrofuran The solution was shaken overnight at room temperature then concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(Propane-2-sulfonyl)-piperazine (0.0286 mmol) was dissolved in 0.25 mL of methylene chloride and added to a solution of 4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (0.024 mmol, example 3) and diisopropylethylamine (0.072 mmol) in. 25 mL of methylene chloride in a 4 mL vial. The vial was capped and shaken overnight at room temperature. The reaction mixture was diluted with 1 mL of methylene chloride and 1 mL of water. The vial was agitated and centrifuged. The organic layer was transferred to a 4 mL vial and concentrated in vacuo to give [4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(propane-2-sulfonyl)-piperazin-1-yl]-methanone. LR-MS (M+H)+=697.4. The vial was capped The vial was agitated concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-BOC-piperazine (0.617 mmol) and diisopropylethylamine (0.679 mmol) in 0.5 mL of methylene chloride was added to a 4 mL vial. Propane-2-sulfonyl chloride (0.679 mmol) was added to the vial, and the reaction mixture was shaken overnight at room temperature. When the reaction was complete, it was diluted with 1.5 mL of methylene chloride and extracted with 1 mL of 1N solution of hydrogen chloride followed by 1 mL of 10% potassium carbonate solution. The organic layer was concentrated in vacuo. The residue was dissolved in 0.5 mL of tetrahydrofuran and 4M solution of hydrogen chloride in dioxane (0.5 mL). The solution was shaken overnight at room temperature then concentrated in vacuo to give 1-(propane-2-sulfonyl)-piperazine. extracted with 1 mL of 1N solution of hydrogen chloride The organic layer was concentrated in vacuo The residue was dissolved in 0.5 mL of tetrahydrofuran The solution was shaken overnight at room temperature then concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Reaction between 2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-carbaldehyde and 1-(propane-2-sulfonyl)-piperazine using procedure C yielded 2-chloro-4-morpholin-4-yl-6-[4-(propane-2-sulfonyl)-piperazin-1-ylmethyl]-thieno[3,2-d]pyrimidine. This compound was subjected to procedure A to yield the desired final compound which was purified using flash chromatography.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Reaction between 2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-carbaldehyde and 1-(propane-2-sulfonyl)-piperazine using procedure C yielded 2-chloro-4-morpholin-4-yl-6-[4-(propane-2-sulfonyl)-piperazin-1-ylmethyl]-thieno[3,2-d]pyrimidine. This compound was subjected to procedure A to yield the desired final compound which was purified using flash chromatography.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of piperazine (1 g) and triethylamine (1.78 mL) in dichloromethane (20 mL) at 0° C. was added dropwise 2-propanesulfonyl chloride (1.30 mL). The reaction mixture was stirred at room temperature for 16 h and then quenched with water (20 mL) and extracted into dichloromethane (2×40 mL). The combined organic layers were washed with saturated aqueous brine solution (2×40 mL), dried (MgSO4) and concentrated to afford 1-(propane-2-sulfonyl)-piperazine as a white solid (1.87 g, 84%). quenched with water (20 mL) extracted into dichloromethane (2×40 mL) The combined organic layers were washed with saturated aqueous brine solution (2×40 mL) dried (MgSO4) concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was synthesized in analogy to example 1, from 5-(4-isopropyl-piperazine-1-carbonyl)-1H-indole-2-carboxylic acid hydrochloride (example 1, intermediate b) and 1-(1-methylethylsulfonyl)piperazine (prepared in analogy to WO2003064413 using isopropylsulfonyl chloride and tert-butyl 1-piperazinecarboxylate) to afford the desired product as a light-brown solid (87%). MS (ISP): 490.3 (M+H)+.