1,1'-Carbonyldiimidazole → 6-(2,4-Dichloro-phenyl)-5-(2-methoxy-ethoxy)-pyrazine-2-carboxylic acid (2-cyclopropyl-2-hydroxy-propyl)-amide

HRID 1865888Notes

Reaction equation

HRID 1865888 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([C:15]([OH:17])=O)[CH:12]=[N:11][C:10]=1[O:18][CH2:19][CH2:20][O:21][CH3:22].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:35][CH2:36][C:37]([CH:40]1[CH2:42][CH2:41]1)([OH:39])[CH3:38]>CN(C)C=O>[CH:40]1([C:37]([OH:39])([CH3:38])[CH2:36][NH:35][C:15]([C:13]2[CH:12]=[N:11][C:10]([O:18][CH2:19][CH2:20][O:21][CH3:22])=[C:9]([C:3]3[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=3[Cl:1])[N:14]=2)=[O:17])[CH2:42][CH2:41]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 211096921-Amino-2-cyclopropylpropan-2-olHCID 688010876-(2,4-Dichloro-phenyl)-5-(2-methoxy-ethoxy)-pyrazine-2-carboxylic acid

Product 1

HCID 866169736-(2,4-Dichloro-phenyl)-5-(2-methoxy-ethoxy)-pyrazine-2-carboxylic acid (2-cyclopropyl-2-hydroxy-propyl)-amideYield 5.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.030 g (0.0009 mol) of 6-(2,4-dichloro-phenyl)-5-(2-methoxy-ethoxy)-pyrazine-2-carboxylic acid in 2.0 ml dimethylformamide was added at room temperature 0.029 g (0.0018 mol) of 1,1′-carbonyldiimidazole and the mixture was stirred at room temperature for 1 hour. To the resulting brown solution was added 0.020 g (0.0018 mol) 1-amino-2-cyclopropyl-propan-2-ol and the mixture was stirred for 3 hours. The reaction mixture was then partitioned between 10% aqueous citric acid and ethyl acetate. The phases were separated and the organic layer washed with 10% aqueous sodium bicarbonate and brine dried over sodium sulfate and evaporated. The residue was purified by chromatography on silica gel using a gradient of heptane to ethyl acetate to yield 0.021 g of the title compound as colorless oil. MS (ISP) (M+H+)=440.4.

Workup

  1. stirringthe mixture was stirred for 3 hours
  2. customThe reaction mixture was then partitioned between 10% aqueous citric acid and ethyl acetate
  3. customThe phases were separated
  4. washthe organic layer washed with 10% aqueous sodium bicarbonate and brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe residue was purified by chromatography on silica gel using a gradient of heptane to ethyl acetate

Sources & evidence

ORD record
ord-67ec9feb8255448386c03359604435de
Source dataset
uspto-grants-2009_12
Patent number
US07629346B2

Reaction notes

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