Tetrabutylammonium Fluoride → 1-benzyl-3-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl}-5-hydroxyiminomethyl-2,4(1H,3H)-pyrimidinedione

HRID 342602Notes

Reaction equation

HRID 342602 reaction equation
Br[CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[O:17][CH3:18])[CH2:7][CH2:6]1.[CH2:19]([N:26]1[CH:31]=[C:30]([CH:32]=[N:33][OH:34])[C:29](=[O:35])[NH:28][C:27]1=[O:36])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(#N)C>[CH2:19]([N:26]1[CH:31]=[C:30]([CH:32]=[N:33][OH:34])[C:29](=[O:35])[N:28]([CH2:2][CH2:3][CH2:4][N:5]2[CH2:10][CH2:9][N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[CH2:7][CH2:6]2)[C:27]1=[O:36])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 612877441-Bromo-3-[4-(2-methoxyphenyl)piperazin-1-yl]propaneHCID 867535631-benzyl-5-hydroxyiminomethyl-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 867535681-benzyl-3-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl}-5-hydroxyiminomethyl-2,4(1H,3H)-pyrimidinedioneYield 17.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 1-bromo-3-[4-(2-methoxyphenyl)piperazin-1-yl]propane (1.09 g, 3.5 mmol), prepared as in Example 25, 1-benzyl-5-hydroxyiminomethyl-2,4(1H,3H)-pyrimidinedione (0.86 g, 3.5 mmol), tetrabutylammonium fluoride (4.5 g, 17.5 mmol) and acetonitrile (50 mL) was stirred 24 hours at 25° C. The reaction mixture then was concentrated in vacuo and the residue was dissolved in ethyl acetate (50 mL). The solution was washed with water (3×50 mL) and brine (1×50 mL) and purified by preparative thin, layer chromatography on silica gel eluting with methylene chloride/methanol (95:5) and 1% ammonium hydroxide to give 1-benzyl-3-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl}-5-hydroxyiminomethyl-2,4(1H,3H)-pyrimidinedione (250 mg, 0.6mmol). The free base was recrystallized from a solution of fumaric acid in alcohol to give 1-benzyl-3-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl}-5-hydroxyiminomethyl-2,4(1H,3H)-pyrimidinedione fumarate, m.p. 198°-200° C.; Anal.: Calcd. for C26H31N5O4.C4H4O4 : C, 59.78; H, 6.02; N, 11.62%; Found: C, 59.74; H, 6.03; N, 11.83%.

Workup

  1. concentrationThe reaction mixture then was concentrated in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate (50 mL)
  3. washThe solution was washed with water (3×50 mL) and brine (1×50 mL)
  4. custompurified by preparative thin, layer chromatography on silica gel eluting with methylene chloride/methanol (95:5) and 1% ammonium hydroxide

Sources & evidence

ORD record
ord-94647cc346c14a66b924f4c092f9da25
Source dataset
uspto-grants-1999_01
Patent number
US05859014

Reaction notes

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