Diisopropylethylamine → 1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid ((S)-1-cyanomethyl-3-methyl-butyl)-amide

HRID 1750173Notes

Reaction equation

HRID 1750173 reaction equation
[CH2:1]([CH:3]([N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]([OH:17])=O)=[CH:14][C:9]=2[N:8]=[C:7]1[CH2:18][C:19]1[S:20][CH:21]=[CH:22][CH:23]=1)[CH2:4][CH3:5])[CH3:2].C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[NH2:44][C@@H:45]([CH2:49][CH:50]([CH3:52])[CH3:51])[CH2:46][C:47]#[N:48].S([O-])(O)(=O)=O.[Na+]>CN(C=O)C.O.C(Cl)CCl>[C:47]([CH2:46][C@@H:45]([NH:44][C:15]([C:13]1[CH:12]=[CH:11][C:10]2[N:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]([CH2:18][C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)=[N:8][C:9]=2[CH:14]=1)=[O:17])[CH2:49][CH:50]([CH3:52])[CH3:51])#[N:48]

Participants

9

Reactant 5

HCID 81531Diisopropylethylamine2×HCID 181649HOAtHCID 516919Sodium BisulfateHCID 867143731-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acidHCID 86714386(S)-3-Amino-5-methyl-hexanenitrile-hydrochloride

Product 1

HCID 867143851-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid ((S)-1-cyanomethyl-3-methyl-butyl)-amideYield 90%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4.93 g of 1-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid in 50 ml of dry DMF 2.04 g of HOAT, 3.45 g of EDC and 4.35 ml of DIPEA were added at 0° C. After 30 min 3.29 g of (S)-3-Amino-5-methyl-hexanenitrile-hydrochloride and 4.35 ml of DIPEA were added and the reaction was stirred at rt for 4 h. The reaction was then poured into water and the pH was adjusted to 3 by the addition of 2 M aqueous sodium hydrogensulphate solution. 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. 5.90 g (90%) of 1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid ((S)-1-cyanomethyl-3-methyl-butyl)-amide 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-5b1693a13d9a454196d244c133826784
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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