Dichloromethane → 5-(3-acetyl-6-cyano-2-ethoxy-5-methylphenyl)-N,N-dimethylpyridine-2-carboxamide

HRID 1499903Notes

Reaction equation

HRID 1499903 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[C:7]([C:10]1[CH:17]=[C:16]([CH3:18])[C:13]([C:14]#[N:15])=[C:12](I)[C:11]=1[O:20][CH2:21][CH3:22])(=[O:9])[CH3:8].[CH3:23][N:24]([CH3:36])[C:25]([C:27]1[N:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)=[O:26].ClCCl>O.C(#N)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:7]([C:10]1[C:11]([O:20][CH2:21][CH3:22])=[C:12]([C:30]2[CH:29]=[CH:28][C:27]([C:25]([N:24]([CH3:36])[CH3:23])=[O:26])=[N:32][CH:31]=2)[C:13]([C:14]#[N:15])=[C:16]([CH3:18])[CH:17]=1)(=[O:9])[CH3:8]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 53438177[6-(Dimethylcarbamoyl)pyridin-3-yl]boronic acidHCID 866778254-Acetyl-3-ethoxy-2-iodo-6-methylbenzonitrile

Product 1

HCID 866778265-(3-acetyl-6-cyano-2-ethoxy-5-methylphenyl)-N,N-dimethylpyridine-2-carboxamideYield 75%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

Sodium carbonate (3 g, 30 mmol) in water (20 mL) was added to a mixture of 4-acetyl-3-ethoxy-2-iodo-6-methylbenzonitrile (3 g, 9 mmol) and {6-[(dimethylamino)carbonyl]pyridin-3-yl}boronic acid (1700 mg, 8.8 mmol, Example 313, Step 2) in acetonitrile (100 mL). The mixture was degassed with nitrogen and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (400 mg, 0.4 mmol) was added. The reaction was degassed again with nitrogen and was heated to 100° C. for 4 hrs. The reaction was allowed to cool to room temperature, diluted with water and extracted with EtOAc. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give the crude product. The product was purified by FCC on silica gel eluting (hexane/EtOAc, 0-100%) gradient to give 5-(3-acetyl-6-cyano-2-ethoxy-5-methylphenyl)-N,N-dimethylpyridine-2-carboxamide product as yellow solid (2.3 g, 75%). LCMS calculated for C20H22N3O3(M+H)+: m/z=352.1; found: 352.2.

Workup

  1. additionwas added
  2. customThe reaction was degassed again with nitrogen
  3. temperatureto cool to room temperature
  4. additiondiluted with water
  5. extractionextracted with EtOAc
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude product
  11. customThe product was purified by FCC on silica gel eluting (hexane/EtOAc, 0-100%) gradient

Sources & evidence

ORD record
ord-04680ddd7c784b08822bee3e40680eb1
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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