Sulfuric acid magnesium salt (1:1) → Flindersine

HRID 1460146Notes

Reaction equation

HRID 1460146 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]([OH:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.S([O-])([O-])(=O)=O.[Mg+2].[CH3:19][C:20]([CH3:24])=[CH:21][CH:22]=O>N1C=CC=CC=1.CO.C(Cl)(Cl)Cl>[CH3:19][C:20]1([CH3:24])[O:12][C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[NH:3][C:2](=[O:1])[C:11]=2[CH:22]=[CH:21]1

Participants

7

Reactant 3

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 610203-Methyl-2-butenal2×HCID 1785165532-hydroxy-1H-quinolin-4-one

Product 1

HCID 68230FlindersineYield 63.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1049PyridineSolventHCID 6212ChloroformSolvent

Procedure

To a boiling solution of 2,4-dihydroxy quinoline (5.0 g, 31 mmol) in pyridine (300 ml) under argon was added anhydrous magnesium sulfate (20 g) followed by 3-methyl-2-butenal (2.6 g, 31.0 mmole). The reaction was heated under reflux for 16 hours. After 12 hours, more 3-methyl-2-butenal (1.3 g, 15.5 mmol) was added and the reaction was heated under reflux for 16 more hours. The reaction was diluted with 10% methanol in chloroform (200 ml) and filtered while hot. The solid was washed with hot solvent (10% methanol in chloroform) and the filtrate was concentrated in vacuo and coevaporated with toluene. The resulting solid was triturated with isopropyl ether to give the title A compound (4.5 g), m.p. 174° C.-177° C.: 1H NMR (DMSO-d6 /CDCl3) ppm: δ7.7 (d, 1H, J =8.0 Hz), 7.4 (d, 1H, J = 9.0 Hz), 7.2 (d, 1H, J =8.0 Hz), 7.1 (dd, 1H, J =7 & 8 Hz), 6.5 (d, 1H, J =8.0 Hz), 5.5 (d, 1H, J =9.0 Hz), 3.3 (s, 1H), 1.34 (2 s, 6H); 13C NMR (DMSO-d6 /CDCl3) ppm: 160.8, 158.7, 136.5, 128.9, 120.9, 120.2, 119.7, 115.0, 113.6, 113.4, 103.7, 76.7, 26.0.

Workup

  1. temperatureThe reaction was heated
  2. temperatureunder reflux for 16 hours
  3. temperaturethe reaction was heated
  4. temperatureunder reflux for 16 more hours
  5. filtrationfiltered while hot
  6. washThe solid was washed with hot solvent (10% methanol in chloroform)
  7. concentrationthe filtrate was concentrated in vacuo
  8. customThe resulting solid was triturated with isopropyl ether

Sources & evidence

ORD record
ord-aa4353fa92ee414d9ae8903dcb107c6b
Source dataset
uspto-grants-1991_12
Patent number
US05070088

Reaction notes

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