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

HRID 504807Notes

Reaction equation

HRID 504807 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:56])[C@@H:33]([CH2:35][S:36][C:37]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[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:56])[C@@H:33]([CH2:35][S:36][C:37]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)([C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=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 574762045-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxylic acidHCID 86619907H-D-Cys(Trt)-OMe*HCl

Product 1

HCID 59135628N-({5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indol-2-yl}carbonyl)-S-trityl-D-cysteine methyl esterYield 72%

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 (0.45 g), S-trityl-D-cysteine methyl ester hydrochloride (0.46 g), 1H-1,2,3-benzotriazol-1-ol (0.26 g), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (0.32 g), triethylamine (0.19 mL) and N,N-dimethylformamide (5 mL) was stirred at room temperature for 64 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 (4:1-1:4, volume ratio) to give the title compound (0.60 g, yield 72%) 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 (4:1-1:4, volume ratio)

Sources & evidence

ORD record
ord-154cc20ba4cd479899dc4245c8e672a1
Source dataset
uspto-grants-2010_08
Patent number
US07777047B2

Reaction notes

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