1-Benzyl-4-piperidylamine → N-(1-benzylpiperidin-4-yl)-5,7-dimethoxy-4-(4-methoxyphenyl)phthalazin-1-amine

HRID 29922

Reaction equation

HRID 29922 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([O:14][CH3:15])[CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)=[N:4][N:3]=1.[NH2:24][CH:25]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:27][CH2:26]1.CC(C)([O-])C.[Na+].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:31]([N:28]1[CH2:29][CH2:30][CH:25]([NH:24][C:2]2[C:11]3[C:6](=[C:7]([O:14][CH3:15])[CH:8]=[C:9]([O:12][CH3:13])[CH:10]=3)[C:5]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)=[N:4][N:3]=2)[CH2:26][CH2:27]1)[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

8

Reactant 4

HCID 4158521-Benzyl-4-piperidylamineHCID 516892Sodium BicarbonateHCID 23676156Sodium t-butoxideHCID 860752924-Chloro-6,8-dimethoxy-1-(4-methoxyphenyl)phthalazine

Product 1

HCID 69213501N-(1-benzylpiperidin-4-yl)-5,7-dimethoxy-4-(4-methoxyphenyl)phthalazin-1-amineYield 46.4%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

400 mg (1.2 mmol) of 4-chloro-6,8-dimethoxy-1-(4-methoxyphenyl)phthalazine dissolved in 5 mL of toluene, 276 mg (1.4 mmol) of 4-amino-1-benzylpiperidine, 163 mg (1.7 mmol) of sodium tert-butoxide, 6 mg (0.009 mmol) of BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) and 5.5 mg (0.006 mmol) of tris(dibenzylideneacetone)dipalladium are successively introduced into a tube under argon. The tube is hermetically sealed and the mixture is stirred at 80° C. for 24 hours. After cooling to room temperature, the reaction medium is hydrolysed with sodium hydrogen carbonate solution and then extracted with ethyl acetate. The organic phase is washed with water and with brine, dried over anhydrous sodium sulfate and then evaporated under reduced pressure. The residue obtained is purified by chromatography on a column of silica gel (solvent: 95/5 (v/v) dichloromethane/methanol). The oily product obtained forms a solid by trituration in ethyl ether. 270 mg of product are obtained in the form of a beige-coloured powder.

Workup

  1. customThe tube is hermetically sealed
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with ethyl acetate
  4. washThe organic phase is washed with water and with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue obtained
  8. customis purified by chromatography on a column of silica gel (solvent: 95/5 (v/v) dichloromethane/methanol)
  9. customThe oily product obtained forms a solid by trituration in ethyl ether

Sources & evidence

ORD record
ord-eb6a4d70ae4842d6ab7efbb824bbfb94
Source dataset
uspto-grants-2008_09
Patent number
US07423030B2

Linked notes

Loading…