Diisopropylamine → 1-[3-(3-Methyl-1,2,4-triazolo[4,3-b]pyridazin-6-yl)phenyl]-2-pyrolidinone

HRID 35642Notes

Reaction equation

HRID 35642 reaction equation
[CH3:1][C:2]1[N:6]2[N:7]=[C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([NH2:17])[CH:12]=3)[CH:9]=[CH:10][C:5]2=[N:4][N:3]=1.C(NC(C)C)(C)C.Cl[CH2:26][CH2:27][CH2:28][C:29](Cl)=[O:30].C(=O)(O)[O-].[Na+]>ClCCl>[CH3:1][C:2]1[N:6]2[N:7]=[C:8]([C:11]3[CH:12]=[C:13]([N:17]4[CH2:26][CH2:27][CH2:28][C:29]4=[O:30])[CH:14]=[CH:15][CH:16]=3)[CH:9]=[CH:10][C:5]2=[N:4][N:3]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 783704-Chlorobutyryl chlorideHCID 516892Sodium BicarbonateHCID 127268683-Methyl-6-[3-(amino)phenyl]-1,2,4-triazolo[4,3-b]pyridazine

Product 1

HCID 155957031-[3-(3-Methyl-1,2,4-triazolo[4,3-b]pyridazin-6-yl)phenyl]-2-pyrolidinone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2 g of 3-methyl-6-[3-(amino)phenyl]-1,2,4-triazolo[4,3-b]pyridazine in 400 ml of dichloromethane was added 1.7 ml of diisopropylamine and 1 ml of 4-chlorobutyryl chloride. This solution was stirred for 12 hours, then poured onto 200 ml of saturated aqueous sodium bicarbonate and extracted with 150 ml portions of dichloromethane. The combined extracts were dried and concentrated in vacuo. The residue was dissolved in 200 ml of dimethylformamide and 2.0 g of potassium carbonate was added. This solution was heated to 80° C. for 12 hours, then poured onto 200 ml of water and extracted with 150 ml portions of dichloromethane. The combined extracts were dried, concentrated in vacuo and chromatographed on 300 g of silica gel with dichloromethane-methanol (97:3). The fractions containing the desired product were combined, concentrated in vacuo and the solid recrystallized from dichloromethane-hexane to give 1.67 g of white crystals, mp 235°-237° C.

Workup

  1. extractionextracted with 150 ml portions of dichloromethane
  2. customThe combined extracts were dried
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in 200 ml of dimethylformamide
  5. addition2.0 g of potassium carbonate was added
  6. additionpoured onto 200 ml of water
  7. extractionextracted with 150 ml portions of dichloromethane
  8. customThe combined extracts were dried
  9. concentrationconcentrated in vacuo
  10. customchromatographed on 300 g of silica gel with dichloromethane-methanol (97:3)
  11. additionThe fractions containing the desired product
  12. concentrationconcentrated in vacuo
  13. customthe solid recrystallized from dichloromethane-hexane

Sources & evidence

ORD record
ord-be58f0768c834b02b294a146bf362bd7
Source dataset
uspto-grants-1988_08
Patent number
US04767765

Reaction notes

Loading…