Formaldehyde → 1-[(3-Methoxy-propylamino)-methyl]-3-(1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one

HRID 492156Notes

Reaction equation

HRID 492156 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[C:2]1/[CH:6]=[C:7]1\[C:8](=[O:16])[NH:9][C:10]2[C:15]\1=[CH:14][CH:13]=[CH:12][CH:11]=2.[CH2:17]=O.[CH3:19][O:20][CH2:21][CH2:22][CH2:23][NH2:24]>CCO.C(Cl)(Cl)Cl>[CH3:19][O:20][CH2:21][CH2:22][CH2:23][NH:24][CH2:17][N:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:7](=[CH:6][C:2]2[NH:1][CH:5]=[CH:4][CH:3]=2)[C:8]1=[O:16]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 16723-MethoxypropylamineHCID 5908088(Z)-3-((1H-pyrrol-2-yl)methylene)indolin-2-one

Product 1

HCID 688377321-[(3-Methoxy-propylamino)-methyl]-3-(1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-oneYield 1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6212ChloroformSolvent

Procedure

A mixture of Z-(1H-Pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one (120.0 mg, 0.571 mmol), paraformaldehyde (17.1 mg, 0.571 mmol), and 3-methoxypropylamine (58.2 μL, 0.571 mmol) in 4.0 mL EtOH was heated at reflux for 6.5 h. The reaction mixture was cooled to room temperature and let stand for 22 h. The reaction mixture was filtered and the filter cake rinsed with 30% ethyl acetate in hexane. The filtrate was concentrated in vacuo and 4 mL of EtOH added. The reaction was refluxed an additional 19.5 h. The reaction mixture was cooled to room temperature and partitioned between 30 mL dilute HCl and 20 mL Ethyl acetate. The organic layer was removed and the aqueous layer washed with 15 mL ethyl acetate. The aqueous layer was made basic to pH 8 with saturated NaHCO3 and extracted with ethyl acetate. The ethyl acetate layer was washed with H2O, brine and dried over anhydrous Na2SO4. The ethyl acetate layer was filtered and then concentrated. The solid obtained (42.5 mg) was dissolved in CHCl3 and purified by chromatography (silica gel, 1:1/hexane:acetone) to give the title compound (1.5 mg, 1%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 6.5 h
  3. filtrationThe reaction mixture was filtered
  4. washthe filter cake rinsed with 30% ethyl acetate in hexane
  5. concentrationThe filtrate was concentrated in vacuo and 4 mL of EtOH
  6. additionadded
  7. temperatureThe reaction was refluxed an additional 19.5 h
  8. temperatureThe reaction mixture was cooled to room temperature
  9. custompartitioned between 30 mL dilute HCl and 20 mL Ethyl acetate
  10. customThe organic layer was removed
  11. washthe aqueous layer washed with 15 mL ethyl acetate
  12. extractionextracted with ethyl acetate
  13. washThe ethyl acetate layer was washed with H2O, brine
  14. dry with materialdried over anhydrous Na2SO4
  15. filtrationThe ethyl acetate layer was filtered
  16. concentrationconcentrated
  17. customThe solid obtained (42.5 mg)
  18. custompurified by chromatography (silica gel, 1:1/hexane:acetone)

Sources & evidence

ORD record
ord-d045dbc0f2da4b32a1e84596af30800f
Source dataset
uspto-grants-2009_05
Patent number
US07531665B2

Reaction notes

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