HOAt → {(3E)-4-[N-((1R)-1-{N-[2-(2-(phenylsulfonylamino)phenyl)ethyl]-N-methylcarbamoyl}2-(2-naphthyl)ethyl)-N-methylcarbamoyl]-1,1-dimethylbut-3-enyl}carbamic acid tert-butyl ester

HRID 582413ノート

反応式

HRID 582413 の反応式
Cl.CN(C)CCCN=C=NCC.[C:13]([O:17][C:18]([NH:20][C:21]([CH3:29])([CH3:28])[CH2:22]/[CH:23]=[CH:24]/[C:25]([OH:27])=O)=[O:19])([CH3:16])([CH3:15])[CH3:14].ON1C2N=CC=CC=2N=N1.[C:40]1([S:46]([NH:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=2[CH2:56][CH2:57][N:58]([CH3:75])[C:59](=[O:74])[C@H:60]([NH:72][CH3:73])[CH2:61][C:62]2[CH:71]=[CH:70][C:69]3[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=3)[CH:63]=2)(=[O:48])=[O:47])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>ClCCl.CN(C)C=O.C(N(C(C)C)C(C)C)C.C(OCC)(=O)C>[C:13]([O:17][C:18](=[O:19])[NH:20][C:21]([CH3:29])([CH3:28])[CH2:22]/[CH:23]=[CH:24]/[C:25](=[O:27])[N:72]([C@@H:60]([C:59](=[O:74])[N:58]([CH2:57][CH2:56][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][C:50]=1[NH:49][S:46]([C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)(=[O:48])=[O:47])[CH3:75])[CH2:61][C:62]1[CH:71]=[CH:70][C:69]2[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=2)[CH:63]=1)[CH3:73])([CH3:14])([CH3:15])[CH3:16]

参加物

9

反応物 4

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10505600(2R)-N-[2-(2-(phenylsulfonylamino)phenyl)ethyl]-N-methyl-2-(methylamino)-3-(2-naphthyl)propionamideHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acid

生成物 1

HCID 59965084{(3E)-4-[N-((1R)-1-{N-[2-(2-(phenylsulfonylamino)phenyl)ethyl]-N-methylcarbamoyl}2-(2-naphthyl)ethyl)-N-methylcarbamoyl]-1,1-dimethylbut-3-enyl}carbamic acid tert-butyl ester収率 69.4%

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 81531Diisopropylethylamine溶媒

反応条件

温度
0 °C

実験手順

{(3E)-4-[N-((1R)-1-{N-[2-(2-(Phenylsulfonylamino)phenyl)ethyl]-N-methylcarbamoyl}-2-2-naphthyl)ethyl)-N-methylcarbamoyl]-1,1-dimethylbut-3-enyl}carbamic acid tert-butyl ester ##STR165## At 0° C., N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (138 mg, 0.72 mmol) was added to a solution of (2E)-5-(tert.-butoxycarbonylamino)-5-methylhex-2-enoic acid (175 mg, 0.72 mmol) and 1-hydroxy-7-azabenzotriazole (98 mg, 0.72 mmol) in dichloromethane (3 ml) and N,N-dimethylformamide (3 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of (2R)-N-[2-(2-(phenylsulfonylamino)phenyl)ethyl]-N-methyl-2-(methylamino)-3-(2-naphthyl)propionamide (363 mg, 0.72 mmol) in dichloromethane (3ml) and ethyldiiso-propylamine (0.13 ml) were added successively. The reaction mixture was stirred for 3 d, while it was warming up to room temperature. It was diluted with ethyl acetate (60 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (60 ml). The aqueous phase was extracted with ethyl acetate (2×30 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (60 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (50 g), using ethyl acetate/heptane 1:1 as eluent, to give 363 mg of {(3E)-4-[N-((1R)-1-{N-[2-(2-(phenylsulfonylamino)phenyl)ethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylcarbamoyl]-1,1-dimethylbut-3-enyl}carbamic acid tert-butyl ester.

後処理

  1. stirringThe reaction mixture was stirred for 3 d, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with a 10% aqueous solution of sodium hydrogen sulfate (60 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×30 ml)
  5. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (60 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified by flash chromatography on silica (50 g)

出典と根拠

ORDレコード
ord-5aa89f40ddfa4abfbeb212437802d1b4
出典データセット
uspto-grants-1999_07
特許番号
US05922770

反応ノート

読み込み中…