Cesium carbonate → Benzophenone [6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]hydrazone

HRID 37886Notes

Reaction equation

HRID 37886 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][N:9]=[C:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:3]=1.[CH3:23][N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[CH3:23][N:24]1[CH2:29][CH2:28][N:27]([C:2]2[N:7]=[CH:6][N:5]=[C:4]([NH:8][N:9]=[C:10]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:3]=2)[CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 531671-Methylpiperazine2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 86672326Benzophenone (6-chloropyrimidin-4-yl)hydrazone

Product 1

HCID 86672327Benzophenone [6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]hydrazone

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×

Conditions

Temperature
120 °C

Procedure

500 mg (1.62 mmol) of the compound from Example 4A, 178 mg (1.78 mmol) of N-methylpiperazine, 58 mg (0.12 mmol) of dicyclohexyl-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine, 22 mg (24 μmol) of tris(dibenzylideneacetone)dipalladium and 1.32 g (4.05 mmol) of cesium carbonate are combined. The mixture is degassed and vented twice with argon, 12.5 ml of a mixture of tert-butanol and toluene (1:5) are added, the mixture is again degassed and vented twice with argon and heated at 120° C. for 24 h. Another 58 mg (0.12 mmol) of dicyclohexyl-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine and 22 mg (24 μmol) of tris(dibenzylideneacetone)dipalladium are then added, the mixture is heated at 120° C. overnight, another 324 mg (3.24 mmol) of N-methylpiperazine are then added and the mixture is heated at 120° C. for a further night. After cooling, the reaction mixture is filtered through kieselguhr, the filtrate is concentrated and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid).

Workup

  1. customThe mixture is degassed
  2. additionare added
  3. customthe mixture is again degassed
  4. temperaturethe mixture is heated at 120° C. overnight
  5. temperaturethe mixture is heated at 120° C. for a further night
  6. temperatureAfter cooling
  7. filtrationthe reaction mixture is filtered through kieselguhr
  8. concentrationthe filtrate is concentrated
  9. customthe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid)

Sources & evidence

ORD record
ord-0d28e8627b2841f290164ef536a43039
Source dataset
uspto-grants-2013_09
Patent number
US08524699B2

Reaction notes

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