Sodium Hydroxide → HCID 17958696, compound

HRID 2217272Notes

Reaction equation

HRID 2217272 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[N:6]([CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1)[CH2:5]2.[CH3:26][N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[OH-].[Na+].[K+].[Br-]>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].C1(C)C=CC=CC=1>[CH3:23][C:22]([CH3:25])([O:21][C:19]([N:16]1[CH2:17][CH2:18][CH:13]([N:6]2[CH2:5][C:4]3[C:9](=[CH:10][CH:11]=[C:2]([N:30]4[CH2:31][CH2:32][N:27]([CH3:26])[CH2:28][CH2:29]4)[CH:3]=3)[NH:8][C:7]2=[O:12])[CH2:14][CH2:15]1)=[O:20])[CH3:24]

Participants

9

Reactant 6

HCID 14798Sodium HydroxideHCID 531671-Methylpiperazine2×HCID 80271Tri-o-tolylphosphine2×HCID 253877Potassium BromideHCID 23676156Sodium t-butoxide2×HCID 69306652HCID 69306652, compound

Product 1

HCID 17958696HCID 17958696, compound

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst2×HCID 1140TolueneSolvent

Procedure

A mixture of 10.0 g (24.372 mmol) of 6-bromo-3,4-dihydro-3-[1-(1,1-dimethylethoxycarbonyl)-4-piperidinyl]-2(1H)-quinazolinone, 2.5 g (24.96 mol) of 1-methylpiperazine, 4.81 g (50.05 mmol) of sodium tert-butoxide, 285 mg (0.4766 mmol) of bis(dibenzylideneacetone)palladium, 305 mg (1.002 mmol) of tris(o-tolyl)phosphine, and 100 mL of toluene was refluxed for 14 hours. After the addition of further equal amounts of 1-methylpiperazine, sodium tert-butoxide, bis(dibenzylideneacetone)palladium, and tris(o-tolyl)phosphine the mixture was refluxed for another 48 hours. The mixture was filtered through activated charcoal and the filtrate was evaporated down in vacuo. The residue was divided between dichloromethane and water. The organic phase was extracted twice with dilute aqueous citric acid solution. The acidic extracts thus obtained were made alkaline with sodium hydroxide and extracted exhaustively with dichloromethane. The combined dichloromethane extracts were evaporated down in vacuo, the residue was purified by column chromatography on silica gel (30-60 μm) using dichloromethane to start with, then methanol/concentrated ammonia 9/1 v/v as eluant. After conventional working up of the appropriate eluates 1.1 g (11% of theoretical) of a colorless substance was obtained. IR (KBr): 1670 (C═O) cm−1; MS: M+=429.

Workup

  1. temperaturewas refluxed for 14 hours
  2. temperaturewas refluxed for another 48 hours
  3. filtrationThe mixture was filtered through activated charcoal
  4. customthe filtrate was evaporated down in vacuo
  5. extractionThe organic phase was extracted twice with dilute aqueous citric acid solution
  6. customThe acidic extracts thus obtained
  7. extractionextracted exhaustively with dichloromethane
  8. customThe combined dichloromethane extracts were evaporated down in vacuo
  9. customthe residue was purified by column chromatography on silica gel (30-60 μm)
  10. customwas obtained

Sources & evidence

ORD record
ord-0cff51f5b01d4eddb8ed5d582ed629d1
Source dataset
uspto-grants-2008_08
Patent number
US07407963B2

Reaction notes

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