Acetic Acid → 5-[3,4-Dichlorophenoxy]-6-methoxy-8-[4-phthalimido-1-methyl-butylamino]lepidine

HRID 842763Notes

Reaction equation

HRID 842763 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([O:22][CH3:23])[C:5]([O:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12].O=[C:25]([CH3:40])[CH2:26][CH2:27][CH2:28][N:29]1[C:33](=[O:34])[C:32]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]2[C:30]1=[O:39].[BH4-].[Na+].[OH-].[Na+].[C:45](O)(=O)C>>[Cl:21][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][C:17]=1[Cl:20])[O:13][C:5]1[C:4]([O:22][CH3:23])=[CH:3][C:2]([NH:1][CH:25]([CH3:40])[CH2:26][CH2:27][CH2:28][N:29]2[C:33](=[O:34])[C:32]3=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]3[C:30]2=[O:39])=[C:11]2[C:6]=1[CH:7]=[CH:8][CH2:9][N:10]2[CH3:45].[Cl:21][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][C:17]=1[Cl:20])[O:13][C:5]1[C:4]([O:22][CH3:23])=[CH:3][C:2]([NH:1][CH:25]([CH3:40])[CH2:26][CH2:27][CH2:28][N:29]2[C:33](=[O:34])[C:32]3=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]3[C:30]2=[O:39])=[C:11]2[C:6]=1[C:7]([CH3:12])=[CH:8][CH:9]=[N:10]2

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 2362702-(4-Oxopentyl)-1H-isoindole-1,3(2H)-dioneHCID 6090148-Amino-5-[3,4-dichlorophenoxy]-6-methoxylepidineHCID 4311764Sodium borohydride

Product 2

HCID 6331175-[3,4-Dichlorophenoxy]-6-methoxy-8-[4-phthalimido-1-methyl-butylamino]lepidineHCID 694641975-(3,4-Dichlorophenoxy)-6-methoxy-1methyl-8-[(4-phthalimido-1-methylbutyl)amino]quinoline

Conditions

Temperature
30 °C

Procedure

A mixture of 12.4 g of 8-amino-5-(3,4-dichlorophenoxy)-6-methoxy-4-methylquinoline (36 mM) and 11.6 g of 4-oxo-1-phthalimidopentane (50 mM), in glacial acetic acid was stirred for 15 min under nitrogen and 2.6 g of sodium borohydride (70 mM) was added portionwise maintaining the temperature 25-35° C. After the addition, the reaction mixture was stirred for 30 min and then poured into ice cold solution of concentrated sodium hydroxide. The resulting precipitate was filtered and chromatographed over silica gel. Elution with hexanes:ethyl acetate 90:10 yielded the expected product of 5-(3,4-dichlorophenoxy)-6-methoxy-4-methyl-8-[(4-phthalimido-1-methylbutyl)amino]quino line which was crystallized from ether to give 12.4 g (22 mM) of yellow crystalline product.

Workup

  1. additionAfter the addition
  2. filtrationThe resulting precipitate was filtered
  3. customchromatographed over silica gel
  4. washElution with hexanes:ethyl acetate 90:10

Sources & evidence

ORD record
ord-21095a23d393418fbcba0e1d862ca66b
Source dataset
uspto-grants-2002_04
Patent number
US06376511B2

Reaction notes

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