Potassium Carbonate → tert-Butyl 2-(5-cyano-2-oxoindolin-3-yl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

HRID 1777189Notes

Reaction equation

HRID 1777189 reaction equation
[O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:11]#[N:12])[CH:8]=2)[NH:3]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[K+].[K+].Cl[C:54]1[CH:63]=[CH:62][C:61]2[CH2:60][N:59]([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:58][CH2:57][C:56]=2[N:55]=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]>[C:11]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[NH:3][C:2](=[O:1])[CH:10]2[C:54]1[CH:63]=[CH:62][C:61]2[CH2:60][N:59]([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:58][CH2:57][C:56]=2[N:55]=1)#[N:12]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrileHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 46835755tert-Butyl 2-chloro-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

Product 1

HCID 66823325tert-Butyl 2-(5-cyano-2-oxoindolin-3-yl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylateYield 59%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

The title compound was prepared as described for Example 1.2 using 2-oxoindoline-5-carbonitrile (59 mg, 0.373 mmol), X-PHOS (14.23 mg, 0.030 mmol), K2CO3 (103 mg, 0.746 mmol), tert-butyl 2-chloro-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (120 mg, 0.448 mmol), and Pd2(dba)3 (6.83 mg, 7.46 μmol). The mixture was heated in a microwave oven at 100° C. for 2 h min. The mixture was cooled to RT and the resulting precipitate was removed by filtration. The remaining residue was dissolved in a mixture of dichloromethane and 2-propanol and the solution was washed with water. The aqueous layer was re-extracted with dichloromethane/2-propanol (3/1, v/v). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and evaporated to dryness. Amount 86 mg. Yield 59%.

Workup

  1. temperatureThe mixture was cooled to RT
  2. customthe resulting precipitate was removed by filtration
  3. dissolutionThe remaining residue was dissolved in a mixture of dichloromethane and 2-propanol
  4. washthe solution was washed with water
  5. extractionThe aqueous layer was re-extracted with dichloromethane/2-propanol (3/1
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated to dryness

Sources & evidence

ORD record
ord-7959e7a7ba7a41f782d23e2262054b2b
Source dataset
uspto-grants-2016_02
Patent number
US09266855B2

Reaction notes

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