N,N-bis(2-chloroethyl)-p-toluenesulphonamide → Methyl (2S)-2-{4-[(4-methylphenyl)sulfonyl]-1-piperazinyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate

HRID 497557

反応式

HRID 497557 の反応式
[NH2:1][C@@H:2]([CH2:7][C:8]1[N:9]=[CH:10][N:11]([C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:12]=1)[C:3]([O:5][CH3:6])=[O:4].Cl[CH2:33][CH2:34][N:35]([CH2:46][CH2:47]Cl)[S:36]([C:39]1[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=1)(=[O:38])=[O:37]>C(N(C(C)C)CC)(C)C.C(#N)C>[CH3:45][C:42]1[CH:43]=[CH:44][C:39]([S:36]([N:35]2[CH2:34][CH2:33][N:1]([C@@H:2]([CH2:7][C:8]3[N:9]=[CH:10][N:11]([C:13]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[CH:12]=3)[C:3]([O:5][CH3:6])=[O:4])[CH2:47][CH2:46]2)(=[O:38])=[O:37])=[CH:40][CH:41]=1

参加物

5

反応物 2

HCID 96039N,N-bis(2-chloroethyl)-p-toluenesulphonamideHCID 7408414H-His(Trt)-OMe

生成物 1

HCID 60030612Methyl (2S)-2-{4-[(4-methylphenyl)sulfonyl]-1-piperazinyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate収率 19%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 81531Diisopropylethylamine溶媒

実験手順

A suspension of methyl (2S)-2-amino-3-(1-trityl-1H-imidazol-4-yl)propanoate (1 g, 2.4 mmol) in diisopropylethylamine (5 ml), was stirred at room temperature for 20 minutes. N,N-Bis(2-chloroethyl)-4-methylbenzenesulfonamide (720 mg, 2.4 mmol) was added and the mixture was stirred at reflux for 3 hours. The mixture was allowed to cool and diluted with acetonitrile. The resultant solution was concentrated under reduced pressure and the residue was suspended in aqueous sodium carbonate solution and extracted with dichloromethane (3×20 ml). The combined organic extracts were washed with brine (3×20 ml), dried (Na2SO4), filtered, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a solvent gradient of dichloromethane:methanol (99:1). The isolated material was dissolved in ether and the resultant solution concentrated under reduced pressure to afford the title compound as a colorless foam, 300 mg, 19% yield.

後処理

  1. stirringthe mixture was stirred
  2. temperatureat reflux for 3 hours
  3. temperatureto cool
  4. concentrationThe resultant solution was concentrated under reduced pressure
  5. extractionextracted with dichloromethane (3×20 ml)
  6. washThe combined organic extracts were washed with brine (3×20 ml)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography on silica gel
  11. washeluting with a solvent gradient of dichloromethane:methanol (99:1)
  12. dissolutionThe isolated material was dissolved in ether
  13. concentrationthe resultant solution concentrated under reduced pressure

出典と根拠

ORDレコード
ord-eda09d4e0eff4cd9866ba262d47e0e6b
出典データセット
uspto-grants-2005_09
特許番号
US06949577B2

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