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

HRID 1373113ノート

反応式

HRID 1373113 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-47d8e52cb0ee463cbf2ce4d61bb37cc4
出典データセット
uspto-grants-2007_01
特許番号
US07160905B2

反応ノート

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