Methyl iodide → HCID 23729329, compound

HRID 1911788Notes

Reaction equation

HRID 1911788 reaction equation
[H-].[Na+].[CH2:3]([N:5]([CH2:40][CH3:41])[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].[CH3:42]I>CN(C=O)C>[CH2:40]([N:5]([CH2:3][CH3:4])[C:6]([C:8]1[N:9]([CH3:42])[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])[CH3:41]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 23729313HCID 23729313, compound

Product 1

HCID 23729329HCID 23729329, compoundYield 68.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (0.01 g, 0.36 mmol) in DMF (5ml) was added 3-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-1H-indole-2-carboxylic acid diethylamide (0.1 g, 0.18 mmol), obtained in Example 131, at 0° C., and stirred for 15 min. Methyl iodide (0.031 g, 0.216 mmol) was added to this at the same temperature. The reaction was stirred for 6 h and 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-methyl-1H-indole-2-carboxylic acid diethylamide (0.07 g, 60%).

Workup

  1. customobtained in Example 131, at 0° C.
  2. stirringThe reaction was stirred for 6 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 15% ethyl acetate and petroleum ether

Sources & evidence

ORD record
ord-a4dbf86818ed43c19dd4c50a4cd5a1d7
Source dataset
uspto-grants-2013_12
Patent number
US08604055B2

Reaction notes

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