1-Hydroxybenzotriazole → 5-Methanesulfonyl-thiophene-2-carboxylic acid [(1S,2S,4R)-1-benzyl-4-(3,3-dimethyl-butylcarbamoyl)-2-hydroxypentyl]-amide

HRID 1373113Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1373113
ON1C2C=CC=CC=2N=N1.ClCCl.CN(C=O)C.[CH3:19][S:20]([C:23]1[S:27][C:26]([C:28]([OH:30])=O)=[CH:25][CH:24]=1)(=[O:22])=[O:21].[CH3:31][C:32]([CH3:53])([CH3:52])[CH2:33][CH2:34][NH:35][C:36](=[O:51])[C@H:37]([CH3:50])[CH2:38][C@H:39]([OH:49])[C@@H:40]([NH2:48])[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>CN(C=O)C.ClCCl>[CH2:41]([C@H:40]([NH:48][C:28]([C:26]1[S:27][C:23]([S:20]([CH3:19])(=[O:21])=[O:22])=[CH:24][CH:25]=1)=[O:30])[C@@H:39]([OH:49])[CH2:38][C@H:37]([C:36](=[O:51])[NH:35][CH2:34][CH2:33][C:32]([CH3:31])([CH3:52])[CH3:53])[CH3:50])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Komponenten

7

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27404975-Methanesulfonylthiophene-2-carboxylic acidHCID 22350042dichloromethane N,N-dimethylformamideHCID 68890142(2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide

Produkt 1

HCID 587808675-Methanesulfonyl-thiophene-2-carboxylic acid [(1S,2S,4R)-1-benzyl-4-(3,3-dimethyl-butylcarbamoyl)-2-hydroxypentyl]-amideAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

N-Cyclohexylcarbodiimide-N′-methyl polystyrene (138 mg @ 1.70 mmol/g; ex. Novabiochem) was treated with dichloromethane (0.5 ml) followed by a solution of 1-hydroxybenzotriazole (32 mg, 0.24 mmol) in 4:1 dichloromethane/DMF (0.5 ml). 5-Methanesulfonyl thiophene-2-carboxylic acid (50 mg, 0.23 mmol) in DMF (0.5 ml) and (2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenyl-hexanoic acid (3,3-dimethylbutyl)-amide (D2) (50 mg, 0.16 mmol) in dichloromethane (0.5 ml) were then added and the mixture was stirred gently overnight at room temperature. It was then diluted with dichloromethane (1 ml) and treated with methylisocyanate polystyrene (150 mg @ 1.80 mmol/g; ex. Novabiochem) and tris-(2-aminoethyl)-amine polystyrene (150 mg @ 3.20 mmol/g; ex. Novabiochem), and the mixture was stirred gently for a further 2 h. It was then filtered and the spent resins were washed with DMF (1 ml) and dichloromethane (1 ml). The combined filtrates were evaporated to dryness and the residue was triturated with diethyl ether to afford the title compound as a white solid (57 mg, 72%).

Aufarbeitung

  1. stirringthe mixture was stirred gently for a further 2 h
  2. filtrationIt was then filtered
  3. washthe spent resins were washed with DMF (1 ml) and dichloromethane (1 ml)
  4. customThe combined filtrates were evaporated to dryness
  5. customthe residue was triturated with diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-47d8e52cb0ee463cbf2ce4d61bb37cc4
Quelldatensatz
uspto-grants-2007_01
Patentnummer
US07160905B2

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