Potassium Carbonate → 3-(5-Methoxy-5,6,7,8-tetrahydroquinolin-2-yl)-2-oxoindoline-5-carbonitrile

HRID 1777200Notes

Reaction equation

HRID 1777200 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.Cl[C:14]1[CH:23]=[CH:22][C:21]2[CH:20]([O:24][CH3:25])[CH2:19][CH2:18][CH2:17][C:16]=2[N:15]=1.C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C(OCC)(=O)C.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].O1CCCC1>[CH3:25][O:24][CH:20]1[CH2:19][CH2:18][CH2:17][C:16]2[N:15]=[C:14]([CH:10]3[C:9]4[C:4](=[CH:5][CH:6]=[C:7]([C:11]#[N:12])[CH:8]=4)[NH:3][C:2]3=[O:1])[CH:23]=[CH:22][C:21]1=2

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrileHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86663637HCID 86663637, compound

Product 1

HCID 569483773-(5-Methoxy-5,6,7,8-tetrahydroquinolin-2-yl)-2-oxoindoline-5-carbonitrileYield 22%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

The title compound was prepared as described for Example 1.2 using 2-oxoindoline-5-carbonitrile (60 mg, 0.379 mmol), 2-chloro-5-methoxy-5,6,7,8-tetrahydroquinoline (90 mg, 0.455 mmol), K2CO3 (105 mg, 0.76 mmol), X-PHOS (14.47 mg, 0.030 mmol), Pd2(dba)3 (6.95 mg, 7.59 μmol), and tetrahydrofuran (1.9 mL). The reaction mixture was heated in a microwave oven at 100° C. for 120 min. After cooling to RT the mixture was diluted with ethyl acetate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were dried over sodium sulfate, filtered, and evaporated to dryness. The crude was purified by flash chromatography (silica gel, dichloromethane/methanol). The product containing fractions were combined, evaporated to dryness, and the resulting solid was triturated with diethylether. Amount 27 mg. Yield 22%.

Workup

  1. temperatureAfter cooling to RT the mixture
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (2×)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe crude was purified by flash chromatography (silica gel, dichloromethane/methanol)
  8. additionThe product containing fractions
  9. customevaporated to dryness
  10. customthe resulting solid was triturated with diethylether

Sources & evidence

ORD record
ord-e6172f602099402c83b73093782b8ede
Source dataset
uspto-grants-2016_02
Patent number
US09266855B2

Reaction notes

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