Cesium carbonate → Ethyl 8-[(4-bromo-2-cyanophenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate

HRID 81947Notes

Reaction equation

HRID 81947 reaction equation
[NH2:1][C:2]1[N:11]=[CH:10][C:9]2[CH2:8][CH2:7][C:6]3[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:13][N:14]([CH3:15])[C:5]=3[C:4]=2[N:3]=1.[Br:21][C:22]1[CH:23]=[CH:24][C:25](I)=[C:26]([CH:29]=1)[C:27]#[N:28].C(=O)([O-])[O-].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.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]>[Br:21][C:22]1[CH:23]=[CH:24][C:25]([NH:1][C:2]2[N:11]=[CH:10][C:9]3[CH2:8][CH2:7][C:6]4[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:13][N:14]([CH3:15])[C:5]=4[C:4]=3[N:3]=2)=[C:26]([C:27]#[N:28])[CH:29]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 70208745-Bromo-2-iodobenzonitrileHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 24993827ethyl 8-amino-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate

Product 1

HCID 67201200Ethyl 8-[(4-bromo-2-cyanophenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylateYield 24.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl 8-amino-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate (207 mg, 0.753 mmol) in dioxane (6 mL), 5-bromo-2-iodobenzonitrile (260 mg, 0.627 mmol) and cesium carbonate (290 mg, 0.753 mmol) were added and the flask was evacuated and backfilled with argon. [Pd2(dba)3] (13 mg, 0.014 mmol) and X-phos (19 mg, 0.033 mmol) were then charged and the mixture was heated at 80° C. under argon for 8 hours. After cooling to room temperature, the reaction mixture was concentrated, suspended in water (10 mL) and extracted with ethyl acetate. The organic phase was anidrified on Na2SO4, filtered and evaporated to dryness, the crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 98/2) to afford 70 mg (20% yield) of the title compound.

Workup

  1. customthe flask was evacuated
  2. temperatureAfter cooling to room temperature
  3. concentrationthe reaction mixture was concentrated
  4. extractionextracted with ethyl acetate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customthe crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 98/2)

Sources & evidence

ORD record
ord-473f89cefa2c4a248db629dae20950d9
Source dataset
uspto-grants-2014_09
Patent number
US08846701B2

Reaction notes

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