Cesium carbonate → 1-[6-Chloro-1-(2-methoxy-ethoxymethyl)-5-nitro-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 408689Notes

Reaction equation

HRID 408689 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:20])[C:15]([N+:17]([O-:19])=[O:18])=[CH:16][C:4]=2[N:3]=1.[CH2:21]([O:23][C:24]([C:26]1[CH:27]=[N:28][NH:29][CH:30]=1)=[O:25])[CH3:22].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH2:21]([O:23][C:24]([C:26]1[CH:27]=[N:28][N:29]([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:20])[C:15]([N+:17]([O-:19])=[O:18])=[CH:16][C:4]=3[N:3]=2)[CH:30]=1)=[O:25])[CH3:22]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 66937039HCID 66937039, compound

Product 1

HCID 669371721-[6-Chloro-1-(2-methoxy-ethoxymethyl)-5-nitro-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl esterYield 99.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2,6-dichloro-1-(2-methoxy-ethoxymethyl)-5-nitro-1H-benzoimidazole (6.15 g, 19.2 mmol), 1H-pyrazole-4-carboxylic acid ethyl ester (2.96 g, 21.1 mmol) and DMF (40 mL) was added cesium carbonate (12.5 g, 38.4 mmol) in a sealable pressure vessel. The vessel was purged with nitrogen, sealed, and heated at 60° C. for 2 h. The reaction mixture was poured into a 1:1 mixture of brine/water (80 mL), and was extracted with EtOAc (3×125 mL). The combined organic layers were washed with brine (3×125 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (5-45% EtOAc/hexanes) to yield the titled compound (8.09 g, 98%) as a mixture of regioisomers. MS (ESI/CI): mass calcd. for C17H18ClN5O6, 423.1; m/z found, 424.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.93 (d, J=0.6 Hz, 1H), 8.28 (s, 1H), 8.22 (d, J=0.6 Hz, 1H), 7.83 (s, 1H), 6.26 (s, 2H), 4.37 (q, J=7.1 Hz, 2H), 3.73-3.67 (m, 2H), 3.49-3.44 (m, 2H), 3.29 (s, 3H), 1.39 (t, J=7.1 Hz, 3H).

Workup

  1. customThe vessel was purged with nitrogen
  2. customsealed
  3. additionThe reaction mixture was poured into a 1:1 mixture of brine/water (80 mL)
  4. extractionwas extracted with EtOAc (3×125 mL)
  5. washThe combined organic layers were washed with brine (3×125 mL)
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified (FCC) (5-45% EtOAc/hexanes)

Sources & evidence

ORD record
ord-59a0143d387e4f16a7153cc5d801606e
Source dataset
uspto-grants-2014_06
Patent number
US08759345B2

Reaction notes

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