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Hydrochloric Acid → 1-{[1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzimidazole-5-carbonyl]-amino}-cycloheptanecarboxylic acid methyl ester

HRID 1750163
Notes
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Reaction equation

HRID 1750163 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.[NH2:44][C:45]1([C:52]([O:54][CH3:55])=[O:53])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1.Cl>CN(C=O)C.O.C(Cl)CCl>[CH3:55][O:54][C:52]([C:45]1([NH:44][C:15]([C:13]2[CH:12]=[CH:11][C:10]3[N:6]([CH:3]([CH2:1][CH3:2])[CH2:4][CH3:5])[C:7]([CH2:18][C:19]4[S:20][CH:21]=[CH:22][CH:23]=4)=[N:8][C:9]=3[CH:14]=2)=[O:16])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1)=[O:53]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2×HCID 181649HOAtHCID 42614177Methyl 1-aminocycloheptane-1-carboxylate hydrochlorideHCID 867143731-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid

Product 1

HCID 86714372
1-{[1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzimidazole-5-carbonyl]-amino}-cycloheptanecarboxylic acid methyl ester
Yield 86.2%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 160 mg of 1-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid (The preparation of intermediates is described below) in 3 ml of dry DMF 73 mg of HOAT, 131 mg of EDC and 0.16 ml of DIPEA were added at 0° C. After 15 min 100 mg of methyl 1-amino-cycloheptanecarboxylate-hydrochloride and 0.16 ml of DIPEA were added and the reaction was stirred at it 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. The crude product was purified by HPLC to yield 200 mg (85%) of 1-{[1-(1-Ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzimidazole-5-carbonyl]-amino}-cycloheptanecarboxylic acid methyl ester.

Workup

  1. additionwere added at 0° C
  2. extractionThe reaction was extracted with ethyl acetate three times
  3. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated
  6. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-58c2a66162b94c7d830468af5a8c3aae
Source dataset
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09156796B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes