Formaldehyde → HCID 68338029, compound

HRID 633982Notes

Reaction equation

HRID 633982 reaction equation
[CH2:1]=O.Cl.[CH3:4][NH:5][CH3:6].[NH:7]1[C:11]2=[N:12][CH:13]=[C:14](/[CH:16]=[CH:17]/[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:15]=[C:10]2[CH:9]=[CH:8]1>C(O)(C)C>[CH3:4][N:5]([CH2:1][C:9]1[C:10]2[C:11](=[N:12][CH:13]=[C:14](/[CH:16]=[CH:17]/[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:15]=2)[NH:7][CH:8]=1)[CH3:6]

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 10473Dimethylamine, hydrochloride2×HCID 68338028HCID 68338028, compound

Product 1

HCID 68338029HCID 68338029, compoundYield 46.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Formaldehyde (37% in water, 219 μL, 2.92 mmol) and dimethylamine hydrochloride (237 mg, 2.92 mmol) were added to a solution of (E)-tert-butyl 3-(1H-pyrrolo[2,3-b]pyridin-5-yl)acrylate (420 mg, 1.72 mmol) in isopropanol (42 mL) at room temperature. The reaction mixture was stirred at reflux overnight. Since the LCMS monitoring still indicated the presence of remaining starting material, formaldehyde (25 μL) and dimethyl amine hydrochloride (28 mg) were added. The reaction mixture was stirred at reflux for an additional 4 hours and concentrated to dryness. The residue was solubilized in an aqueous solution of potassium carbonate (3N, 100 mL) and the solution was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with a saturated solution of sodium chloride (50 mL), dried over sodium sulfate, filtered and concentrated to dryness. The crude was triturated in pentane to give the title compound as a white solid (242 mg, 46%).

Workup

  1. temperatureat reflux overnight
  2. additionwere added
  3. stirringThe reaction mixture was stirred
  4. temperatureat reflux for an additional 4 hours
  5. concentrationconcentrated to dryness
  6. extractionthe solution was extracted with ethyl acetate (3×100 mL)
  7. washThe combined organic layers were washed with a saturated solution of sodium chloride (50 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customThe crude was triturated in pentane

Sources & evidence

ORD record
ord-224a9bea67c5487e8716a660a1e19f5e
Source dataset
uspto-grants-2016_04
Patent number
US09321769B2

Reaction notes

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