1-(2-methylsulfonylethyl)piperazine;dihydrochloride

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

実験手順: 2-{4-[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(3-ethoxy-thiophen-2-yl)-4,5-dihydro-imidazole-1-carbonyl chloride was reacted with 1-(2-methanesulfonylethyl)piperazine dihydrochloride (example 3) to give [(4S,5R)-4,5-bis-(4-chloro-phenyl)-2-(3-ethoxy-thiophen-2-yl)-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone in an analogous manner as described in example 1. LR-MS: 635.1 [(M+H)+].

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

実験手順: cis-4-[2-(2-tert-Butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 20) was reacted with 1-(2-methanesulfonyl-ethyl)piperazine dihydrochloride (example 3) to give cis-[2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone hydrochloride in an analogous manner as described in example 1. HR-MS (ES, m/z) calculated for C33H41N6O4SCl2 [(M+H)+] 687.2282, observed 687.2286.

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

実験手順: cis-4-[4,5-Bis-(4-chloro-phenyl)-2-(4-ethoxy-2-methyl-pyrimidin-5-yl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 16) was reacted with 1-(2-methanesulfonyl-ethyl)piperazine dihydrochloride (example 3) to give cis-[4,5-bis-(4-chloro-phenyl)-2-(4-ethoxy-2-methyl-pyrimidin-5-yl)-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone in an analogous manner as described in example 1. HR-MS (ES, m/z) calculated for C30H34N6O4SCl2 [(M+H)+] 645.1812, observed 645.1814.

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

実験手順: cis-4-[4,5-Bis-(4-chloro-phenyl)-2-(4-ethoxy-2-methylsulfanyl-pyrimidin-5-yl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 12) was reacted with 1-(2-methanesulfonylethyl)-piperazine dihydrochloride (example 3) to give cis-[4,5-bis-(4-chloro-phenyl)-2-(4-ethoxy-2-methylsulfanyl-pyrimidin-5-yl)-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone in an analogous manner as described in example 1. HR-MS (ES, m/z) calculated for C30H35N6O4S2Cl2 [(M+H)+] 677.1533, observed 677.1532.

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

実験手順: cis-4-[4,5-Bis-(4-chloro-phenyl)-2-(2,4-diethoxy-pyrimidin-5-yl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 8) was reacted with 1-(2-methanesulfonylethyl)-piperazine dihydrochloride (example 3) to give cis-[4,5-bis-(4-chloro-phenyl)-2-(2,4-diethoxy-pyrimidin-5-yl)-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone in an analogous manner as described in example 1. HR-MS (ES, m/z) calculated for C31H37N6O5SCl2 [(M+H)+] 675.1918, observed 675.1914.

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

実験手順: cis-4-[4,5-Bis-(4-chloro-phenyl)-2-(4-ethoxy-2-trifluoromethyl-pyrimidin-5-yl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 5) was reacted with 1-(2-methanesulfonylethyl)piperazine dihydrochloride (example 3) to give cis-[4,5-bis-(4-chloro-phenyl)-2-(4-ethoxy-2-trifluoromethyl-pyrimidin-5-yl)-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone in an analogous manner as described in example 1. HR-MS (ES, m/z) calculated for C30H32N6O4SF3Cl2 [(M+H)+] 699.1530, observed 699.1533.

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

実験手順: cis-4-[4,5-Bis-(4-chloro-phenyl)-2-(4-ethoxy-2-trifluoromethyl-pyrimidin-5-yl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 5) was reacted with 1-(2-methanesulfonylethyl)piperazine dihydrochloride (example 3) to give cis-[4,5-bis-(4-chloro-phenyl)-2-(4-ethoxy-2-trifluoromethyl-pyrimidin-5-yl)-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone in an analogous manner as described in example 1. HR-MS (ES, m/z) calculated for C30H32N6O4SF3Cl2 [(M+H)+] 699.1530, observed 699.1533.

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

実験手順: 4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-pyridin-3-yl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 1) was reacted with 1-(2-methanesulfonylethyl)piperazine dihydrochloride to give cis-[4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-pyridin-3-yl)-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone in an analogous manner as described in example 1. HR-MS (ES, m/z) calculated for C30H34N5O4SCl2 [(M+H)+] 630.1703, observed 603.1705.

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

実験手順: 4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-pyridin-3-yl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 1) was reacted with 1-(2-methanesulfonylethyl)piperazine dihydrochloride to give cis-[4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-pyridin-3-yl)-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone in an analogous manner as described in example 1. HR-MS (ES, m/z) calculated for C30H34N5O4SCl2 [(M+H)+] 630.1703, observed 603.1705.

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

実験手順: Hydrochloric acid (42 mL, 168 mmol, 4 M in 1,4-dioxane) was added to a cooled solution of 1-tert-butyloxycarbonyl-4-(2-methanesulfonylethyl)piperazine (2.29 g, 7.8 mmol) in 1,4-dioxane (42 mL). The mixture was stirred at room temperature overnight then concentrated to give 1-(2-methanesulfonylethyl)piperazine dihydrochloride as a white solid (2.05 g). then concentrated

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

実験手順: cis-4,5-Bis-(4-chloro-phenyl)-2-[4-(1-diethylcarbamoyl-1-methyl-ethyl)-2-ethoxy-phenyl]-4,5-dihydro-imidazole-1-carbonyl chloride (27 mg, 0.0439 mmol) was reacted with 1-(2-methanesulfonyl-ethyl)piperazine dihydrochloride (17.5 mg, 0.0659 mmol, example 17) using the procedure described in example 25 to give cis-2-(4-{4,5-bis-(4-chloro-phenyl)-1-[4-(2-methanesulfonyl-ethyl)-piperazine-1-carbonyl]-4,5-dihydro-1H-imidazol-2-yl}-3-ethoxy-phenyl)-N,N-diethyl-isobutyramide (29.5 mg, 87% yield) as white solids. HR-MS (ES, m/z): observed 770.2909, calculated for C39H50Cl2N5O5S [(M+H)+] 770.2904.

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

実験手順: cis-4,5-Bis-(4-chloro-phenyl)-2-[4-(1-diethylcarbamoyl-1-methyl-ethyl)-2-ethoxy-phenyl]-4,5-dihydro-imidazole-1-carbonyl chloride (27 mg, 0.0439 mmol) was reacted with 1-(2-methanesulfonyl-ethyl)piperazine dihydrochloride (17.5 mg, 0.0659 mmol, example 17) using the procedure described in example 25 to give cis-2-(4-{4,5-bis-(4-chloro-phenyl)-1-[4-(2-methanesulfonyl-ethyl)-piperazine-1-carbonyl]-4,5-dihydro-1H-imidazol-2-yl}-3-ethoxy-phenyl)-N,N-diethyl-isobutyramide (29.5 mg, 87% yield) as white solids. HR-MS (ES, m/z): observed 770.2909, calculated for C39H50Cl2N5O5S [(M+H)+] 770.2904.