Triethylamine → 6-(6-Methoxy-4-methyl-8-quinolylamino)-N-(2-methyl-1-propyl)hexanamide

HRID 1863126Notes

Reaction equation

HRID 1863126 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([O:13][CH3:14])[CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12].Br[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([NH:23][CH2:24][CH:25]([CH3:27])[CH3:26])=[O:22].C(N(CC)CC)C>C(OCC)(=O)C>[CH3:14][O:13][C:4]1[CH:5]=[C:6]2[C:11](=[C:2]([NH:1][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([NH:23][CH2:24][CH:25]([CH3:26])[CH3:27])=[O:22])[CH:3]=1)[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 6047536-Methoxy-4-methyl-8-quinolinamineHCID 203934276-bromo-N-(2-methyl-1-propyl)-hexanamide

Product 1

HCID 203934326-(6-Methoxy-4-methyl-8-quinolylamino)-N-(2-methyl-1-propyl)hexanamideYield 60.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A stirred mixture of 22.6 g (0.120 mole) of 8-amino-6-methoxy-4-methylquinoline and 29.6 g (0.118 mole) of 6-bromo-N-(2-methyl-1-propyl)-hexanamide was heated in an oil bath (130° ) while 12.2 g (16.8 ml; 0.120 mole) of triethylamine was added dropwise over 30 minutes. The temperature of the bath was kept at 130° for 30 minutes, at 150° for 60 minutes, between 150° and 190° for 30 minutes, and at 190° for 30 minutes. The mixture was cooled to room temperature then diluted with 25 ml of ethyl acetate. The solid that separated was collected on a filter, extracted with boiling ethyl acetate (3×100 ml), then discarded. The filtrate and extracts were combined, then concentrated in vacuo to a solid; yield 44 g. The solid was dissolved in 130 ml of dichloromethane and purified by elution chromatography on a column (8 cm dia× 40 cm) of silica gel (1000 g; activity III) using 1 l of dichloromethane-ether (1:1), followed by 2 l of ether, as eluents. The fractions (100 ml each) containing pure product were combined then concentrated in vacuo. The fractions containing mixtures were concentrated in vacuo then triturated with diethyl ether to yield 25.4 g (60.2%) of crude product. The product was suitable for further transformation. Analytically pure compound was readily obtained (84% recovery) by recrystallization from methylene chloride and ether; mp 111°-112°.

Workup

  1. additionwas added dropwise over 30 minutes
  2. waitat 190° for 30 minutes
  3. customThe solid that separated
  4. customwas collected on a filter
  5. extractionextracted with boiling ethyl acetate (3×100 ml)
  6. concentrationconcentrated in vacuo to a solid
  7. dissolutionThe solid was dissolved in 130 ml of dichloromethane
  8. custompurified by elution chromatography on a column (8 cm dia× 40 cm) of silica gel (1000 g; activity III)
  9. additionThe fractions (100 ml each) containing pure product
  10. concentrationwere combined then concentrated in vacuo
  11. additionThe fractions containing mixtures
  12. concentrationwere concentrated in vacuo
  13. customthen triturated with diethyl ether

Sources & evidence

ORD record
ord-aa0bf535757a496083a0a3375cb005fd
Source dataset
uspto-grants-1979_09
Patent number
US04167638

Reaction notes

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