Dimethylformamide → 7-(2-{[Di-tert-butyl(phenyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxamide

HRID 1188890Notes

Reaction equation

HRID 1188890 reaction equation
[C:1]([Si:5]([C:40]([CH3:43])([CH3:42])[CH3:41])([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[O:6][CH2:7][CH:8]([CH3:33])[O:9][C:10]1[CH:11]=[C:12]([O:22][C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=2)[CH:13]=[C:14]2[C:18]=1[NH:17][C:16]([C:19]([OH:21])=O)=[CH:15]2)([CH3:4])([CH3:3])[CH3:2].Cl.C[N:46](C)CCCN=C=NCC.[NH4+].ON1C2C=CC=CC=2N=N1.CN(C)C=O>CCCCCC.C(OCC)(=O)C>[C:1]([Si:5]([C:40]([CH3:43])([CH3:42])[CH3:41])([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[O:6][CH2:7][CH:8]([CH3:33])[O:9][C:10]1[CH:11]=[C:12]([O:22][C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=2)[CH:13]=[C:14]2[C:18]=1[NH:17][C:16]([C:19]([NH2:46])=[O:21])=[CH:15]2)([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 220338091-Hydroxybenzotriazole, ammonium saltHCID 668982647-(2-{[Di-tert-butyl(phenyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylic acid

Product 1

HCID 668983707-(2-{[Di-tert-butyl(phenyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxamideYield 69%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 7-(2-{[di-tert-butyl(phenyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylic acid (2.0 g), 1-[3-(dimethylamino)propyl-3-ethylcarbodiimide hydrochloride (1.19 g), 1-hydroxybenzotriazole ammonium salt (943 mg) and N,N-dimethylformamide (20 mL) was stirred at room temperature for 9 hr. The reaction solution was allowed to cool to room temperature, and concentrated under reduced pressure. Water was added to the residue, and the mixture was subjected to extraction with ethyl acetate. The organic layer was washed successively with aqueous citric acid solution, water and saturated brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (ethyl acetate:hexane=30:70-70:30, volume ratio) to give the title compound (1.37 g, yield 69%) as an orange oil. MS 643 (MH+).

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated under reduced pressure
  3. additionWater was added to the residue
  4. extractionthe mixture was subjected to extraction with ethyl acetate
  5. washThe organic layer was washed successively with aqueous citric acid solution, water and saturated brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe obtained crude product

Sources & evidence

ORD record
ord-0a3fdaafbc974b78b6d59f3e7f7f0bdc
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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