HCID 71001800, compound → HCID 71001818, compound

HRID 2274465Notes

Reaction equation

HRID 2274465 reaction equation
[NH2:1][C:2]1[N:3]([CH2:19][CH3:20])[C:4]2[C:9]([C:10](=[O:17])[C:11]=1[C:12]1[NH:13][CH:14]=[CH:15][N:16]=1)=[CH:8][CH:7]=[C:6](I)[CH:5]=2.[OH:21][C@@:22]([CH3:28])([CH2:25][O:26][CH3:27])[C:23]#[CH:24]>CN(C=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Cu](I)I>[NH2:1][C:2]1[N:3]([CH2:19][CH3:20])[C:4]2[C:9]([C:10](=[O:17])[C:11]=1[C:12]1[NH:13][CH:14]=[CH:15][N:16]=1)=[CH:8][CH:7]=[C:6]([C:24]#[C:23][C@:22]([OH:21])([CH3:28])[CH2:25][O:26][CH3:27])[CH:5]=2

Participants

6

Reactant 2

HCID 71001800HCID 71001800, compoundHCID 86714578HCID 86714578, compound

Product 1

HCID 71001818HCID 71001818, compound

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

0.43 mg (1.15 mmol) of 2-amino-1-ethyl-3-(1H-imidazol-2-yl)-7-iodo-1H-quinolin-4-one, 0.262 (23 mmol) of (R)-3-hydroxy-4-methoxy-3-methyl-but-1-yne, and 0.397 g (3.45 mmol) were mixed in 15 ml of DMF. Argon was flushed through this solution for 10 minutes. After addition of 0.126 mg (0.17 mmol) of 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride and 0.033 mg (0.17 mmol) of copper iodide, the reaction mixture was stirred at 80° C. during 6 hours. The reaction mixture was then evaporated to dryness and the residue poured into a mixture of DCM and water. A black insoluble solid was filtered off (100 mg). The aqueous phase was extracted three times with dichloromethane. The combined organic phases were dried over MgSO4 and the solvents were evaporated off under reduced pressure. The residue was then purified by column chromatography (DCM/MeOH/NH4OH aq: 9/1/0.1) to yield 0.80 g (1.2 mmol) of yellow solid. This solid was recrystallized in dichloromethane to yield 0.02 g of a beige solid.

Workup

  1. customArgon was flushed through this solution for 10 minutes
  2. customThe reaction mixture was then evaporated to dryness
  3. additionthe residue poured into a mixture of DCM and water
  4. filtrationA black insoluble solid was filtered off (100 mg)
  5. extractionThe aqueous phase was extracted three times with dichloromethane
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. customthe solvents were evaporated off under reduced pressure
  8. customThe residue was then purified by column chromatography (DCM/MeOH/NH4OH aq: 9/1/0.1)

Sources & evidence

ORD record
ord-13a6932fd9954f11b40d5d9c440814e3
Source dataset
uspto-grants-2015_09
Patent number
US09126972B2

Reaction notes

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