Hydrochloric Acid → (S)-2-{[1-(1-Ethyl-propyl)-2-(tetrahydro-furan-2-ylmethyl)-1H-benzoimidazole-5-carbonyl]-amino}-4-methyl-pentanoic acid tert-butyl ester

HRID 1750165Notes

Reaction equation

HRID 1750165 reaction equation
[CH2:1]([CH:3]([N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15](O)=[O:16])=[CH:14][C:9]=2[N:8]=[C:7]1[CH2:18][CH:19]1[CH2:23][CH2:22][CH2:21][O:20]1)[CH2:4][CH3:5])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[C:44]([O:48][C:49](=[O:56])[C@H:50]([CH2:52][CH:53]([CH3:55])[CH3:54])[NH2:51])([CH3:47])([CH3:46])[CH3:45].Cl>CN(C=O)C.O.C(Cl)CCl>[C:44]([O:48][C:49](=[O:56])[C@@H:50]([NH:51][C:15]([C:13]1[CH:12]=[CH:11][C:10]2[N:6]([CH:3]([CH2:1][CH3:2])[CH2:4][CH3:5])[C:7]([CH2:18][CH:19]3[CH2:23][CH2:22][CH2:21][O:20]3)=[N:8][C:9]=2[CH:14]=1)=[O:16])[CH2:52][CH:53]([CH3:54])[CH3:55])([CH3:46])([CH3:45])[CH3:47]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 12451443tert-butyl (2S)-2-amino-4-methylpentanoate hydrochlorideHCID 867143751-(1-Ethyl-propyl)-2-(tetrahydro-furan-2-ylmethyl)-1H-benzoimidazole-5-carboxylic acid

Product 1

HCID 86714374(S)-2-{[1-(1-Ethyl-propyl)-2-(tetrahydro-furan-2-ylmethyl)-1H-benzoimidazole-5-carbonyl]-amino}-4-methyl-pentanoic acid tert-butyl esterYield 88.8%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 55 mg of 1-(1-Ethyl-propyl)-2-(tetrahydro-furan-2-ylmethyl)-1H-benzoimidazole-5-carboxylic acid in 1 ml of dry DMF 26 mg of HOBT, 37 mg of EDC and 0.05 ml of DIPEA were added at 0° C. After 15 min 100 mg of L-leucine tert-butyl ester-hydrochloride and 0.05 ml of DIPEA were added and the reaction was stirred at rt for 16 h. The reaction was then poured into water and the pH was adjusted to 3 by the addition of 2 M aqueous hydrochloric acid. The reaction was extracted with ethyl acetate three times. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulphate and concentrated. 75 mg (88%) of (S)-2-{[1-(1-Ethyl-propyl)-2-(tetrahydro-furan-2-ylmethyl)-1H-benzoimidazole-5-carbonyl]-amino}-4-methyl-pentanoic acid tert-butyl ester were obtained.

Workup

  1. extractionThe reaction was extracted with ethyl acetate three times
  2. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-e192452960a240c29cc578b5538b690e
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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