Dimethylformamide → HCID 66937166, compound

HRID 538113Notes

Reaction equation

HRID 538113 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]=[CH:14][CH:15]=[C:16]([Cl:17])[C:4]=2[N:3]=1.CN(C=O)C.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:29]([O:31][C:32]([C:34]1[CH:35]=[N:36][NH:37][CH:38]=1)=[O:33])[CH3:30]>[Cl-].[Na+].O>[CH2:29]([O:31][C:32]([C:34]1[CH:35]=[N:36][N:37]([C:2]2[N:6]([CH2:7][O:8][CH2:9][CH2:10][O:11][CH3:12])[C:5]3[CH:13]=[CH:14][CH:15]=[C:16]([Cl:17])[C:4]=3[N:3]=2)[CH:38]=1)=[O:33])[CH3:30]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 66937230HCID 66937230, compound

Product 1

HCID 66937166HCID 66937166, compound

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2,4-dichloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazole (0.660 g, 2.40 mmol) and DMF (10 mL), was added Cs2CO3 (1.88 g, 5.76 mmol) and 1H-pyrazole-4-carboxylic acid ethyl ester (0.400 g, 2.88 mmol). The resulting mixture was then heated to 80° C. for 2 h. The mixture was cooled to 23° C., poured into brine (40 mL), and extracted with EtOAc (3×40 mL). The combined organic layers were washed with brine (40 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (10-50% EtOAc/hexanes) to yield the titled compound as a mixture of regioisomers (0.880 g, 97%). MS (ESI/CI): mass calcd. for C17H19ClN4O4, 378.1; m/z found, 379.1 [M+H]+. 1H NMR (500 MHz, CDCl3): 8.97 (s, 1H), 8.80 (s, 1H), 8.22 (s, 1H), 8.20 (s, 1H), 7.65 (s, 1H), 7.53 (s, 1H), 7.40-7.23 (m, 4H), 6.38 (s, 2H), 6.16 (s, 2H), 4.41-4.31 (m, 4H), 3.68-3.59 (m, 2H), 3.57-3.49 (m, 2H), 3.48-3.41 (m, 2H), 3.41-3.35 (m, 2H), 3.31 (s, 3H), 3.25 (s, 3H), 1.38 (td, J=7.1, 1.2 Hz, 6H).

Workup

  1. temperatureThe mixture was cooled to 23° C.
  2. extractionextracted with EtOAc (3×40 mL)
  3. washThe combined organic layers were washed with brine (40 mL)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified (FCC) (10-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-3cfbe869bf354eebb56fe6ead35e07ba
Source dataset
uspto-grants-2014_10
Patent number
US08865713B2

Reaction notes

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