rel-(2R,6S)-2,6-dimethylpiperazine → 1-[2-(cis-3,5-Dimethylpiperazin-1-yl)ethyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

HRID 1818794ノート

反応式

HRID 1818794 の反応式
Br[CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[S:5]1(=[O:20])=[O:19].[CH3:21][C@H:22]1[CH2:27][NH:26][CH2:25][C@@H:24]([CH3:28])[NH:23]1>C(O)C>[CH3:21][C@H:22]1[NH:23][C@@H:24]([CH3:28])[CH2:25][N:26]([CH2:2][CH2:3][N:4]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[N:6]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[S:5]2(=[O:20])=[O:19])[CH2:27]1

参加物

4

反応物 2

HCID 6950261rel-(2R,6S)-2,6-dimethylpiperazineHCID 687112711-(2-Bromoethyl)-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

生成物 1

HCID 578862581-[2-(cis-3,5-Dimethylpiperazin-1-yl)ethyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide収率 70%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
90 °C

実験手順

A mixture of 1-(2-bromoethyl)-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (212 mg, 0.600 mmol), cis-2,6-dimethylpiperazine (411 mg, 3.60 mmol, 6 equiv.) and ethanol (5 mL) in a sealed reaction vessel was heated at 90° C. for 8 h. After cooling, solvent was removed, and the residue was dissolved in ethyl acetate (15 mL). The resulting solution was washed with an aqueous potassium carbonate solution, water, dried (anhydrous sodium sulfate), and concentrated. The crude oil was pre-adsorbed onto Florisil and purified via Isco flash column chromatography (4-g redisep silica gel column, 1-18% methanol/dichloromethane, with 1% triethylamine as eluent additive) to give 162 mg (70%) of 1-[2-(cis-3,5-dimethylpiperazin-1-yl)ethyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide as a viscous, colorless liquid. This free base was dissolved in ethanol (2 mL), and was treated with an ethereal solution of hydrochloric acid (1 M, 3.0 mL, 3.0 mmol in ethyl ether). To the resulting solution was added ethyl ether until it became cloudy, then cooled to −25° C. in a freezer overnight. The white crystals formed was collected, washed with hexane, and dried in vacuo to yield 176 mg of 1-[2-(cis-3,5-dimethylpiperazin-1-yl)ethyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide dihydrochloride. HRMS: calculated for C20H26N4O2S+H+, 387.1849; found (ESI, [M+H]+), 387.1861.

後処理

  1. customin a sealed reaction vessel
  2. temperatureAfter cooling
  3. customsolvent was removed
  4. dissolutionthe residue was dissolved in ethyl acetate (15 mL)
  5. washThe resulting solution was washed with an aqueous potassium carbonate solution, water
  6. dry with materialdried (anhydrous sodium sulfate)
  7. concentrationconcentrated
  8. custompurified via Isco flash column chromatography (4-g redisep silica gel column, 1-18% methanol/dichloromethane, with 1% triethylamine as eluent additive)

出典と根拠

ORDレコード
ord-95bf1a9feed444aa88fe1660bfdbe65c
出典データセット
uspto-grants-2009_10
特許番号
US07601722B2

反応ノート

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