1-Hydroxybenzotriazole → N-[2-(benzylthio)-3,3-dimethoxypropyl]-5-(2-methoxyethoxy)-7-(methyl[(1-methyl-1H-imidazol-2-yl)sulfonyl]amino}-1H-indole-2-carboxamide

HRID 1960417Notes

Reaction equation

HRID 1960417 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([N:15]([CH3:25])[S:16]([C:19]3[N:20]([CH3:24])[CH:21]=[CH:22][N:23]=3)(=[O:18])=[O:17])[CH:14]=1)[NH:11][C:10]([C:26](O)=[O:27])=[CH:9]2.[CH2:29]([S:36][CH:37]([CH:40]([O:43][CH3:44])[O:41][CH3:42])[CH2:38][NH2:39])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CCCCCC.C(OCC)(=O)C.CN(C)C=O>[CH2:29]([S:36][CH:37]([CH:40]([O:41][CH3:42])[O:43][CH3:44])[CH2:38][NH:39][C:26]([C:10]1[NH:11][C:12]2[C:8]([CH:9]=1)=[CH:7][C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:14][C:13]=2[N:15]([CH3:25])[S:16]([C:19]1[N:20]([CH3:24])[CH:21]=[CH:22][N:23]=1)(=[O:17])=[O:18])=[O:27])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 574759902-(Benzylthio)-3,3-dimethoxypropan-1-amineHCID 591356465-(2-methoxyethoxy)-7-(methyl[(1-methyl-1H-imidazol-2-yl)sulfonyl]amino}-1H-indole-2-carboxylic acid

Product 1

HCID 59135861N-[2-(benzylthio)-3,3-dimethoxypropyl]-5-(2-methoxyethoxy)-7-(methyl[(1-methyl-1H-imidazol-2-yl)sulfonyl]amino}-1H-indole-2-carboxamideYield 89.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-(2-methoxyethoxy)-7-{methyl[(1-methyl-1H-imidazol-2-yl)sulfonyl]amino}-1H-indole-2-carboxylic acid (2.3 g), 2-(benzylthio)-3,3-dimethoxypropan-1-amine (1.7 g), 1H-1,2,3-benzotriazol-1-ol (1.2 g), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (1.6 g) and N,N-dimethylformamide (70 mL) was stirred at room temperature for 14 hr. The reaction solution was concentrated under reduced pressure, ethyl acetate and water were added, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water, aqueous citric acid solution, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over magnesium sulfate, and filtrated, and the filtrate was concentrated under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (ethyl acetate:hexane=20:80-80:20) to give the title compound (3.2 g, yield 89%) as a colorless oil.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure, ethyl acetate and water
  2. additionwere added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed successively with water, aqueous citric acid solution, saturated aqueous sodium hydrogencarbonate solution and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltrated
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe obtained crude product

Sources & evidence

ORD record
ord-f21d7ae93a2e44e8be88d526a33d72c3
Source dataset
uspto-grants-2013_04
Patent number
US08410087B2

Reaction notes

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