Dimethylformamide → HCID 66937322, compound

HRID 408711Notes

Reaction equation

HRID 408711 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:25])[C:15]([S:17][C:18]3[CH:19]=[C:20]([CH3:24])[CH:21]=[CH:22][CH:23]=3)=[CH:16][C:4]=2[N:3]=1.CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:37]([O:39][C:40]([C:42]1[CH:43]=[N:44][NH:45][CH:46]=1)=[O:41])[CH3:38]>[Cl-].[Na+].O>[CH2:37]([O:39][C:40]([C:42]1[CH:43]=[N:44][N:45]([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:25])[C:15]([S:17][C:18]4[CH:19]=[C:20]([CH3:24])[CH:21]=[CH:22][CH:23]=4)=[CH:16][C:4]=3[N:3]=2)[CH:46]=1)=[O:41])[CH3:38]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 66937304HCID 66937304, compound

Product 1

HCID 66937322HCID 66937322, compound

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2,6-dichloro-1-(2-methoxy-ethoxymethyl)-5-m-tolylsulfanyl-1H-benzoimidazole (0.500 g, 1.26 mmol) and DMF (2.52 mL) was added cesium carbonate (0.820 g, 2.52 mmol) and 1H-pyrazole-4-carboxylic acid ethyl ester (0.194 g, 1.38 mmol). The mixture was heated at 80° C. for 2 h in a sealed tube. The mixture was cooled to 23° C. and poured into brine (40 mL), and extracted with EtOAc (3×50 mL). The organic layers were washed with brine (40 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (0-50% EtOAc/hexanes) to yield the titled compound as a 1:1 mixture of regioisomers (0.387 g, 61%). 1H NMR (500 MHz, CDCl3): 8.84 (s, 1H), 8.79 (s, 1H), 8.14 (s, 2H), 7.77 (s, 1H), 7.68 (s, 1H), 7.44 (s, 1H), 7.41 (s, 1H), 7.23-7.18 (m, 4H), 7.18-7.16 (m, 1H), 7.12 (d, J=7.6 Hz, 2H), 7.09 (d, J=7.5 Hz, 1H), 6.09 (s, 2H), 5.98 (s, 2H), 4.36-4.27 (m, 4H), 3.66-3.60 (m, 2H), 3.55-3.50 (m, 2H), 3.48-3.42 (m, 2H), 3.38-3.34 (m, 2H), 3.28 (s, 3H), 3.24 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H), 1.38-1.30 (m, 6H).

Workup

  1. temperatureThe mixture was cooled to 23° C.
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe organic layers were washed with brine (40 mL)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified (FCC) (0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-cd4e326bbc964b65a09723866a13fa73
Source dataset
uspto-grants-2014_06
Patent number
US08759345B2

Reaction notes

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