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

HRID 408764Notes

Reaction equation

HRID 408764 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-ab112ca8415c4f05aa396742d29108d3
Source dataset
uspto-grants-2014_06
Patent number
US08759345B2

Reaction notes

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