Glycol monoethyl ether → 4-Methyl-5-(3-trifluoromethylphenoxy)-6-methoxy-8-(4-phthalimido-1-methylbutylamino)quinoline

HRID 1388567Notes

Reaction equation

HRID 1388567 reaction equation
[CH3:1][C:2]1[C:11]2[C:6](=[C:7]([NH2:25])[CH:8]=[C:9]([O:23][CH3:24])[C:10]=2[O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[N:5]=[CH:4][CH:3]=1.I[CH:27]([CH3:42])[CH2:28][CH2:29][CH2:30][N:31]1[C:35](=[O:36])[C:34]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]2[C:32]1=[O:41].C(N(CC)CC)C.C(OCCO)C>C(Cl)(Cl)Cl>[CH3:1][C:2]1[C:11]2[C:6](=[C:7]([NH:25][CH:27]([CH3:42])[CH2:28][CH2:29][CH2:30][N:31]3[C:35](=[O:36])[C:34]4=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]4[C:32]3=[O:41])[CH:8]=[C:9]([O:23][CH3:24])[C:10]=2[O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:20])([F:21])[F:22])[CH:14]=2)[N:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8076Glycol monoethyl etherHCID 8471Triethylamine2×HCID 123682034-Iodo-1-phthalimido-pentane2×HCID 130042034-Methyl-5-(3-trifluoromethylphenoxy)-6-methoxy-8-aminoquinoline

Product 1

HCID 130042054-Methyl-5-(3-trifluoromethylphenoxy)-6-methoxy-8-(4-phthalimido-1-methylbutylamino)quinolineYield 34%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of the above-8-aminoquinoline (VII 3.0 g, 8.6 mmol), 4-iodo-1-phthalimidopentane (IPP) 3.0 g, 8.7 mmol), triethylamine (TEA) (1.2 mL) and 2-ethoxyethanol (6 mL) was heated at 105° for 2.5 hours, after which time an additional quantity of IPP (3 g) and TEA (1.2 mL) was added. After an additional 4 hours at 105°, the mixture was cooled and dissolved in chloroform. The chloroform solution was washed with 10% aqueous potassium hydroxide and with water, dried and concentrated to dryness. The residue was dissolved in ether and excess ethereal HCL was added. The ether was decanted and the gum was triturated in fresh ether (×2). The gum was then shaken with ether and 10% aqueous potassium carbonate. The ether was removed and the residue was heated in ethanol (15 mL). The mixture was cooled and the solid was filtered to give 1.65 g of the title compound. The filtrate was concentrated to dryness and the residue was triturated in hot ligroin (bp 60°-80°, 50 mL). The ligroin was decanted from a little insoluble gum and concentrated to dryness to afford 1.5 g of additional crude product. The combined crops were crystallized from ethanol (75 mL) to give 2.75 g (57%) of pure title compound, mp 143°-145°.

Workup

  1. temperaturewas heated at 105° for 2.5 hours
  2. temperaturethe mixture was cooled
  3. washThe chloroform solution was washed with 10% aqueous potassium hydroxide and with water
  4. customdried
  5. concentrationconcentrated to dryness
  6. dissolutionThe residue was dissolved in ether
  7. additionexcess ethereal HCL was added
  8. customThe ether was decanted
  9. customthe gum was triturated in fresh ether (×2)
  10. customThe ether was removed
  11. temperaturethe residue was heated in ethanol (15 mL)
  12. temperatureThe mixture was cooled
  13. filtrationthe solid was filtered

Sources & evidence

ORD record
ord-e4616393c27c4d318dc2186e0a5c3d75
Source dataset
uspto-grants-1984_02
Patent number
US04431807

Reaction notes

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