Sodium hydride → HCID 23729312, compound

HRID 1911786Notes

Reaction equation

HRID 1911786 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[NH:9][C:10]2[C:15]([C:16]=1[CH2:17][N:18]([CH2:25][C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=1)[C:19]1[N:20]=[N:21][N:22]([CH3:24])[N:23]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH3:4].[CH:40]1([C:43](Cl)=[O:44])[CH2:42][CH2:41]1>CN(C=O)C>[CH2:3]([O:5][C:6]([C:8]1[N:9]([C:43]([CH:40]2[CH2:42][CH2:41]2)=[O:44])[C:10]2[C:15]([C:16]=1[CH2:17][N:18]([CH2:25][C:26]1[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=1)[C:19]1[N:20]=[N:21][N:22]([CH3:24])[N:23]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 77637Cyclopropanecarbonyl chlorideHCID 23729292HCID 23729292, compound

Product 1

HCID 23729312HCID 23729312, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (0.004 g, 0.18 mmol) in DMF (5 mL) was added 3-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-1H-indole-2-carboxylic acid ethyl ester (0.05 g, 0.095 mmol), obtained in step (vi) of Example 1, at 0° C., and stirred for 15 min. Cyclopropanecarbonyl chloride (0.012 g, 0.11 mmol) was added to this at the same temperature and the reaction was stirred for 6 h. The aqueous layer was extracted with ethyl acetate (3×20 mL).The combined organic layers were washed with brine, dried over sodium sulphate and then concentrated under vacuum to afford the crude residue which was purified by column chromatography over 100-200 mesh silica gel using 15% ethyl acetate and petroleum ether to afford 3-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-1-cyclopropanecarbonyl-1H-indole-2-carboxylic acid ethyl ester (0.04 g, yield: 71%).

Workup

  1. customobtained in step (vi) of Example 1, at 0° C.
  2. stirringthe reaction was stirred for 6 h
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×20 mL).The combined organic layers
  4. washwere washed with brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated under vacuum
  7. customto afford the crude residue which
  8. customwas purified by column chromatography over 100-200 mesh silica gel using 15% ethyl acetate and petroleum ether

Sources & evidence

ORD record
ord-1c19b5c77ab64d2a9cecd93ae71efeb1
Source dataset
uspto-grants-2013_12
Patent number
US08604055B2

Reaction notes

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