1-Hydroxybenzotriazole → N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethylbutylcarbamoyl)-2-hydroxypentyl]-3-methanesulfonyl-benzamide

HRID 1373109Notes

Reaction equation

HRID 1373109 reaction equation
ON1C2C=CC=CC=2N=N1.ClCCl.CN(C=O)C.[CH3:19][S:20]([C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26]([OH:28])=O)(=[O:22])=[O:21].[CH3:32][C:33]([CH3:54])([CH3:53])[CH2:34][CH2:35][NH:36][C:37](=[O:52])[C@H:38]([CH3:51])[CH2:39][C@H:40]([OH:50])[C@@H:41]([NH2:49])[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C=O)C.ClCCl>[CH2:42]([C@H:41]([NH:49][C:26](=[O:28])[C:25]1[CH:29]=[CH:30][CH:31]=[C:23]([S:20]([CH3:19])(=[O:21])=[O:22])[CH:24]=1)[C@@H:40]([OH:50])[CH2:39][C@H:38]([C:37](=[O:52])[NH:36][CH2:35][CH2:34][C:33]([CH3:32])([CH3:53])[CH3:54])[CH3:51])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 2203803-Methanesulfonylbenzoic acidHCID 22350042dichloromethane N,N-dimethylformamideHCID 68890142(2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide

Product 1

HCID 58780868N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethylbutylcarbamoyl)-2-hydroxypentyl]-3-methanesulfonyl-benzamideYield 49%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

N-Cyclohexylcarbodiimide-N′-methyl polystyrene (100 mg @ 1.70 mmol/g; ex. Novabiochem) was treated with dichloromethane (0.5 ml) followed by a solution of 1-hydroxybenzotriazole (22 mg, 0.14 mmol) in 4:1 dichloromethane/DMF (0.5 ml). 3-Methanesulfonyl benzoic acid (28 mg, 0.14 mmol) in DMF (0.5 ml) and (2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide (D2) (30 mg, 0.094 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 (0.5 ml) and treated with methylisocyanate polystyrene (100 mg @ 1.80 mmol/g; ex. Novabiochem) and tris-(2-aminoethyl)-amine polystyrene (100 mg @ 3.20 mmol/g; ex. Novabiochem), and the mixture was stirred gently for a further 1.5 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/hexane to afford the title compound (E1) as a white solid (23 mg, 49%).

Workup

  1. stirringthe mixture was stirred gently for a further 1.5 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/hexane

Sources & evidence

ORD record
ord-87dec13e40ca4ffaaad39c6dfecd0c64
Source dataset
uspto-grants-2007_01
Patent number
US07160905B2

Reaction notes

Loading…