Sodium Hydroxide → 4-[6-[[6-Methoxy-4-methyl-8-quinolinyl]amino]hexyl]-1-piperazinepropanol

HRID 542836Notes

Reaction equation

HRID 542836 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH:11][CH2:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([NH:28][C:29]2[CH:30]=[C:31]([O:40][CH3:41])[CH:32]=[C:33]3[C:38]=2[N:37]=[CH:36][CH:35]=[C:34]3[CH3:39])=O)[CH2:17][CH2:16]1.[OH-].[Na+]>O1CCCC1.O>[CH3:41][O:40][C:31]1[CH:32]=[C:33]2[C:38](=[C:29]([NH:28][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][N:18]3[CH2:19][CH2:20][N:15]([CH2:14][CH2:13][CH2:12][OH:11])[CH2:16][CH2:17]3)[CH:30]=1)[N:37]=[CH:36][CH:35]=[C:34]2[CH3:39]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 6451240Aluminum(III) ChlorideHCID 202071744-(3-hydroxypropyl)-N-(6-methoxy-4-methyl-8-quinolinyl)-1-piperazinehexanamideHCID 21226445Aluminium lithium hydride

Product 1

HCID 5355704-[6-[[6-Methoxy-4-methyl-8-quinolinyl]amino]hexyl]-1-piperazinepropanolYield 49.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A cold (-40°) slurry of 1.8 g (0.0135 mole) of anhydrous aluminum chloride in 60 ml of tetrahydrofuran was added to an equally cold suspension of 1.5 g (0.039 mole) of lithium aluminum hydride in 30 ml of tetrahydrofuran. The mixture was stirred and allowed to warm to -10°. To it was added dropwise a solution of 4.4 g (0.0103 mole) of 4-(3-hydroxypropyl)-N-(6-methoxy-4-methyl-8-quinolinyl)-1-piperazinehexanamide in 15 ml of tetrahydrofuran. The mixture was stirred for 2 hr, then treated with 7 ml of 30% sodium hydroxide solution and enough water to clarify the supernatant and finally filtered through supercell. The filtrate was concentrated in vacuo to remove tetrahydrofuran, diluted with dichloromethane, washed with water, dried, and concentrated to dryness. The residue was chromatographed over 200 g of silica gel with a 15:84:1 mixture of methanol:ethyl acetate-triethylamine. That portion of the eluant containing the product, Rf(silica--25:74:1 mixture of methanol:ethyl acetate:triethylamine)=0.33, was concentrated to dryness in vacuo. Recrystallization of the residue from 2-propanol afforded 2.1 g (49%) of the title compound, mp 100°-102°.

Workup

  1. temperatureto warm to -10°
  2. stirringThe mixture was stirred for 2 hr
  3. filtrationfinally filtered through supercell
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto remove tetrahydrofuran
  6. additiondiluted with dichloromethane
  7. washwashed with water
  8. customdried
  9. concentrationconcentrated to dryness
  10. customThe residue was chromatographed over 200 g of silica gel with a 15:84:1 mixture of methanol
  11. additionThat portion of the eluant containing
  12. additionthe product, Rf(silica--25:74:1 mixture of methanol:ethyl acetate:triethylamine)=0.33
  13. concentrationwas concentrated to dryness in vacuo
  14. customRecrystallization of the residue from 2-propanol

Sources & evidence

ORD record
ord-7bb0b933c88c49f69802ee9225e87411
Source dataset
uspto-grants-1987_04
Patent number
US04659708

Reaction notes

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