Ethyl formimidate hydrochloride → HCID 178423647, compound

HRID 1498010Notes

Reaction equation

HRID 1498010 reaction equation
Cl.[CH:2](=[NH:6])OCC.[CH3:7][C:8]1[N:9]([NH2:26])[CH:10]=[C:11]([C:13]2[CH:14]=[N:15][N:16]([CH3:25])[C:17]=2[C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)[N:12]=1>C(O)C>[CH3:7][C:8]1[N:9]([NH:26][CH:2]=[NH:6])[CH:10]=[C:11]([C:13]2[CH:14]=[N:15][N:16]([CH3:25])[C:17]=2[C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)[N:12]=1

Participants

4

Reactant 2

HCID 12578842Ethyl formimidate hydrochloride3×HCID 681818812-methyl-4-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-1H-imidazol-1-amine

Product 1

HCID 178423647HCID 178423647, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

Ethyl imidoformate hydrochloride (608 mg, 5.55 mmol) was added to a solution of 2-methyl-4-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-1H-imidazol-1-amine (148 mg, 0.554 mmol) in ethanol (5 mL), and the reaction mixture was heated at 75° C. for 66 hours. Additional ethyl imidoformate hydrochloride (300 mg, 2.74 mmol) was added, and heating was continued for 8 hours. A final charge of ethyl imidoformate hydrochloride (300 mg, 2.74 mmol) was followed by maintaining the reaction at 75° C. for an additional 18 hours. The reaction mixture was cooled, concentrated in vacuo and diluted with ethyl acetate. This organic layer was washed with saturated aqueous sodium bicarbonate solution, washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. Filtration and removal of solvent under reduced pressure, followed by purification using silica gel chromatography (Eluant: 10% methanol in dichloromethane) provided the product as a yellow solid. Yield: 70 mg, 0.24 mmol, 43%. LCMS m/z 295.5 (M+1). 1H NMR (400 MHz, CD3OD), presumed to be a mixture of rotamers or tautomers: δ 2.20 and 2.25 (2 s, 3H), 2.43 (br s, 3H), 3.68 (s, 3H), 6.14 and 6.30 (2 s, 1H), 7.26-7.30 (m, 3H), 7.35 (br d, J=8 Hz, 2H), 7.84 and 7.81 (2 s, 1H).

Workup

  1. temperatureheating
  2. temperatureby maintaining
  3. customthe reaction at 75° C. for an additional 18 hours
  4. temperatureThe reaction mixture was cooled
  5. concentrationconcentrated in vacuo
  6. additiondiluted with ethyl acetate
  7. washThis organic layer was washed with saturated aqueous sodium bicarbonate solution
  8. washwashed with saturated aqueous sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. filtrationFiltration and removal of solvent under reduced pressure
  11. customfollowed by purification

Sources & evidence

ORD record
ord-ced357f199c54b6e85d9b3aca255a0be
Source dataset
uspto-grants-2015_12
Patent number
US09200000B2

Reaction notes

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