Triethylamine → HCID 59421785, compound

HRID 499909Notes

Reaction equation

HRID 499909 reaction equation
[OH:1][CH2:2][CH2:3][O:4][C:5]([C:7]1[N:8]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=2)[CH:9]=[C:10]([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=2[CH3:23])=[O:14])[N:11]=1)=[O:6].C(N(CC)CC)C.[Br:42][CH2:43][C:44](Cl)=[O:45].C(=O)(O)[O-].[Na+]>ClCCl.CN(C=O)C.CN(C1C=CN=CC=1)C>[Br:42][CH2:43][C:44]([O:1][CH2:2][CH2:3][O:4][C:5]([C:7]1[N:8]([CH2:24][C:25]2[CH:26]=[CH:27][C:28]([C:31]([F:33])([F:32])[F:34])=[CH:29][CH:30]=2)[CH:9]=[C:10]([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=2[CH3:23])=[O:14])[N:11]=1)=[O:6])=[O:45]

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 89602Bromoacetyl chloride2×HCID 516892Sodium BicarbonateHCID 59421794HCID 59421794, compound

Product 1

HCID 59421785HCID 59421785, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1 g (2 mmol) of 2-hydroxyethyl-4-({[(4-chloro-2-methylphenyl)amino]carbonyl}amino)-1-[4-(trifluoromethyl)benzyl]-1H-imidazole-2-carboxylate (Example 125) are dissolved in a mixture of 25 ml of dichloromethane and 12 ml of DMF, and 1570 μl (1.14 g, 11.2 mmol) of triethylamine are added. While cooling in ice, 804 μl (1.52 g, 9.6 mmol) of bromoacetyl chloride and a catalytic amount of DMAP are added. After stirring at RT for 16 h, a further 0.57 g (5.6 mmol) of triethylamine, 0.76 g (4.8 mmol) of bromoacetyl chloride and a few crystals of DMAP are added while cooling in ice. The reaction mixture is stirred at RT for 2.5 h, poured into saturated sodium bicarbonate solution and extracted twice with ethyl acetate. The combined extracts are washed twice with water and once with saturated sodium chloride solution, dried with magnesium sulphate and evaporated in vacuo. The residue from evaporation is purified by chromatography on silica gel with dichloromethane/methanol as eluent.

Workup

  1. additionare added
  2. temperatureWhile cooling in ice
  3. temperaturewhile cooling in ice
  4. stirringThe reaction mixture is stirred at RT for 2.5 h
  5. extractionextracted twice with ethyl acetate
  6. washThe combined extracts are washed twice with water and once with saturated sodium chloride solution
  7. dry with materialdried with magnesium sulphate
  8. customevaporated in vacuo
  9. customThe residue from evaporation
  10. customis purified by chromatography on silica gel with dichloromethane/methanol as eluent

Sources & evidence

ORD record
ord-d4fc9144788244c9a0c8e3e3e695eb3b
Source dataset
uspto-grants-2010_08
Patent number
US07767704B2

Reaction notes

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