Dimethylformamide → 1-[4,5,6-Trichloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 538196Notes

Reaction equation

HRID 538196 reaction equation
Cl[C:2]1[N:6]([CH2:7][O:8][CH2:9][CH2:10][O:11][CH3:12])[C:5]2[CH:13]=[C:14]([Cl:19])[C:15]([Cl:18])=[C:16]([Cl:17])[C:4]=2[N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:26]([O:28][C:29]([C:31]1[CH:32]=[N:33][NH:34][CH:35]=1)=[O:30])[CH3:27].CN(C=O)C>CCOC(C)=O>[CH2:26]([O:28][C:29]([C:31]1[CH:32]=[N:33][N:34]([C:2]2[N:6]([CH2:7][O:8][CH2:9][CH2:10][O:11][CH3:12])[C:5]3[CH:13]=[C:14]([Cl:19])[C:15]([Cl:18])=[C:16]([Cl:17])[C:4]=3[N:3]=2)[CH:35]=1)=[O:30])[CH3:27]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 669374782,4,5,6-Tetrachloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazole

Product 1

HCID 669370881-[4,5,6-Trichloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2,4,5,6-tetrachloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazole (0.275 g, 0.80 mmol), Cs2CO3 (0.524 g, 1.61 mmol), 1H-pyrazole-4-carboxylic acid ethyl ester (0.124 g, 0.89 mmol), and DMF (4 mL) was heated to 80° C. for 2 h. The mixture was cooled to 23° C. EtOAc was added and the mixture was washed with brine. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified (FCC) to yield the titled compound as a mixture of regioisomers (0.166 g, 46%). MS (ESI/CI): mass calcd. for C17H17Cl3N4O4, 446.0; m/z found, 447.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 9.01-8.97 (m, 2H), 8.40 (t, J=2.3 Hz, 1H), 8.37 (s, 1H), 8.21 (s, 1H), 8.13 (s, 1H), 6.09 (s, 2H), 6.01 (s, 2H), 4.30 (qd, J=7.1 Hz, 2.9, 8H), 3.58-3.51 (m, 2H), 3.44 (d, J=4.9 Hz, 2H), 3.11 (s, 3H), 3.08 (s, 3H), 1.32 (tt, J=7.1 Hz, 1.7 Hz, 6H).

Workup

  1. temperatureThe mixture was cooled to 23° C
  2. washthe mixture was washed with brine
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified (FCC)

Sources & evidence

ORD record
ord-f86613c79c2249169b479a49c6d241ab
Source dataset
uspto-grants-2014_10
Patent number
US08865713B2

Reaction notes

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