Dimethylamine → HCID 68882648, compound

HRID 1785120Notes

Reaction equation

HRID 1785120 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH2:13][CH2:14][O:15][CH3:16])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[CH3:35][NH:36][CH3:37]>C(O)C>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH2:13][CH2:14][O:15][CH3:16])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:36]([CH3:37])[CH3:35])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1

Participants

4

Reactant 2

HCID 674DimethylamineHCID 68882290HCID 68882290, compound

Product 1

HCID 68882648HCID 68882648, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

N-[5-Chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (200 mg, 0.40 mmol) and dimethylamine (5 ml of a 33% solution in ethanol) were stirred and heated under reflux at 90° for 30 min. before evaporating the solution. A further 5 ml of dimethylamine solution were added to the residue and the solution heated for a further 90 min. then evaporated. Again a further 5 ml of dimethylamine solution were added to the residue and the solution heated for 1 hr. before quenching in water and extracting with dichloromethane. The extract was washed with saturated brine, dried over magnesium sulphate and evaporated to an orange oil. It was then purified by column chromatography on silica using increasing concentrations of methanolic ammonia in dichloromethane as eluent. There was thus obtained the title compound (156 mg, 77%) as a pale orange solid; NMR Spectrum:(DMSOd6) 1.95 (quintet, 2H), 2.17 (s, 6H), 2.38 (t, 2H), 2.71 (t, 2H), 3.30 (s, 3H), 3.52 (t, 2H), 3.92 (s, 3H), 4.17 (t, 2H), 6.14 (s, 2H), 7.07 (s, 1H), 7.17 (s, 1H), 7.81 (s, 1H), 8.31 (s, 1H), 9.50 (s, 1H); Mass Spectrum: M+H+ 513/515.

Workup

  1. temperatureheated
  2. temperatureunder reflux at 90° for 30 min.
  3. custombefore evaporating the solution
  4. additionA further 5 ml of dimethylamine solution were added to the residue
  5. temperaturethe solution heated for a further 90 min.
  6. customthen evaporated
  7. additionAgain a further 5 ml of dimethylamine solution were added to the residue
  8. temperaturethe solution heated for 1 hr
  9. custombefore quenching in water
  10. extractionextracting with dichloromethane
  11. washThe extract was washed with saturated brine
  12. dry with materialdried over magnesium sulphate
  13. customevaporated to an orange oil
  14. customIt was then purified by column chromatography on silica using
  15. temperatureincreasing concentrations of methanolic ammonia in dichloromethane as eluent

Sources & evidence

ORD record
ord-7c883de606af43868ac1be7d94f5896d
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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