1-Hydroxybenzotriazole → S-benzyl-N-({5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indol-2-yl)carbonyl)-L-cysteine methyl ester

HRID 504805Notes

Reaction equation

HRID 504805 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[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)(=[O:18])=[O:17])[CH:14]=1)[NH:11][C:10]([C:26]([OH:28])=O)=[CH:9]2.Cl.[CH3:30][O:31][C:32](=[O:44])[C@H:33]([CH2:35][S:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[NH2:34].N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.C(N(CC)CC)C>[CH3:30][O:31][C:32](=[O:44])[C@H:33]([CH2:35][S:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[NH:34][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[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)(=[O:18])=[O:17])=[O:28]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 45073222h-Cys(bzl)-ome.hclHCID 574762045-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxylic acid

Product 1

HCID 59136110S-benzyl-N-({5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indol-2-yl)carbonyl)-L-cysteine methyl esterYield 96.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxylic acid (3.00 g), S-benzyl-L-cysteine methyl ester hydrochloride (1.90 g), 1H-1,2,3-benzotriazol-1-ol (1.70 g), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (2.10 g), triethylamine (1.50 mL) and N,N-dimethylformamide (40 mL) was stirred at room temperature for 18 hr. The reaction mixture was concentrated, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (1:1-1:2, volume ratio) to give the title compound (4.30 g, yield 94%) as a colorless amorphous solid.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionwater was added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. washeluted with hexane-ethyl acetate (1:1-1:2, volume ratio)

Sources & evidence

ORD record
ord-841bab9b9f374f1e953dd7250f496cc4
Source dataset
uspto-grants-2010_08
Patent number
US07777047B2

Reaction notes

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