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

HRID 1750185Notes

Reaction equation

HRID 1750185 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.[CH3:44][NH:45][S:46]([CH2:49][C@@H:50]([NH2:55])[CH2:51][CH:52]([CH3:54])[CH3:53])(=[O:48])=[O:47].Cl>CN(C=O)C.O.C(Cl)CCl>[CH3:53][CH:52]([CH3:54])[CH2:51][C@H:50]([NH:55][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][S:46](=[O:48])(=[O:47])[NH:45][CH3:44]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 867143731-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acidHCID 86714400(S)-2-Amino-4-methyl-pentane-1-sulfonic acid methylamide-hydrochloride

Product 1

HCID 867144031-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid ((S)-3-methyl-1-methylsulfamoylmethyl-butyl)-amide

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 80 mg of 1-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid in 0.5 ml of dry DMF 17 mg of HOAT, 56 mg of EDC and 0.24 ml of DIPEA were added at 0° C. After 15 min 60 mg of (S)-2-Amino-4-methyl-pentane-1-sulfonic acid methylamide-hydrochloride were added and the reaction was stirred at it for 20 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 2 M aqueous hydrochloric acid, saturated sodium bicarbonate solution and brine, dried over magnesium sulphate and concentrated. After purification by HPLC 55 mg (45%) of 1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid ((S)-3-methyl-1-methylsulfamoylmethyl-butyl)-amide were obtained.

Workup

  1. extractionThe reaction was extracted with ethyl acetate three times
  2. washThe combined organic phases were washed with 2 M aqueous hydrochloric acid, saturated sodium bicarbonate solution and brine
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated
  5. customAfter purification by HPLC 55 mg (45%) of 1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid ((S)-3-methyl-1-methylsulfamoylmethyl-butyl)-amide
  6. customwere obtained

Sources & evidence

ORD record
ord-a1684393630d48e8a117ccab0549df33
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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