1-Bromopropane → HCID 23729294, compound

HRID 1911784Notes

Reaction equation

HRID 1911784 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].Br[CH2:41][CH2:42][CH3:43]>CN(C=O)C>[CH2:3]([O:5][C:6]([C:8]1[N:9]([CH2:41][CH2:42][CH3:43])[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 78401-BromopropaneHCID 24758Sodium hydrideHCID 23729292HCID 23729292, compound

Product 1

HCID 23729294HCID 23729294, compoundYield 703.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (0.23 g, 1.9 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 (0.03 g, 0.05 mmol), obtained in step (vi) of Example 124, at 0° C., and stirred for 15 min. Bromopropane (0.23 g, 1.9 mmol) was added to this at the same temperature and the reaction was stirred for another 1 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 10% ethyl acetate and pet ether to afford 3-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-1-propyl-1H-indole-2-carboxylic acid ethyl ester (0.2 g, yield: 38%).

Workup

  1. customobtained in step (vi) of Example 124, at 0° C.
  2. stirringthe reaction was stirred for another 1 h
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×20 mL)
  4. washThe combined organic layers were 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 10% ethyl acetate and pet ether

Sources & evidence

ORD record
ord-be7fbf899b1b4ab39adebdf4903a2c20
Source dataset
uspto-grants-2013_12
Patent number
US08604055B2

Reaction notes

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