Hydrochloric Acid → HCID 178446088, compound

HRID 1750182Notes

Reaction equation

HRID 1750182 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][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][CH:45]([CH3:58])[CH2:46][C@H:47]([NH2:57])[CH2:48][S:49]([C:52]1[NH:56][CH:55]=[N:54][N:53]=1)(=[O:51])=[O:50].Cl>CN(C=O)C.O.C(Cl)CCl>[CH3:44][CH:45]([CH3:58])[CH2:46][C@H:47]([NH:57][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:16])[CH2:48][S:49]([C:52]1[NH:56][CH:55]=[N:54][N:53]=1)(=[O:51])=[O:50]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 867143731-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acidHCID 178446058HCID 178446058, compound

Product 1

HCID 178446088HCID 178446088, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 120 mg of 1-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid in 1 ml of dry DMF 25 mg of HOAT, 85 mg of EDC and 0.36 ml of DIPEA were added at 0° C. After 15 min 108 mg of (S)-3-Methyl-1-(4H-[1,2,4]triazole-3-sulfonylmethyl)-butylamine-hydrochloride were added and the reaction was stirred at rt 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 163 mg (82%) of 1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid [(S)-3-methyl-1-(4H-[1,2,4]-triazole-3-sulfonylmethyl)-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 163 mg (82%) of 1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid [(S)-3-methyl-1-(4H-[1,2,4]-triazole-3-sulfonylmethyl)-butyl]-amide
  6. customwere obtained

Sources & evidence

ORD record
ord-6d4e2e31892c43df945746e917b5df02
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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