Nitrogen → 5-(3-acetyl-5-chloro-6-cyano-2-methoxyphenyl)-N,N-dimethylpyridine-2-carboxamide

HRID 1499896Notes

Reaction equation

HRID 1499896 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[C:7]([C:10]1[CH:17]=[C:16]([Cl:18])[C:13]([C:14]#[N:15])=[C:12](Br)[C:11]=1[O:20][CH3:21])(=[O:9])[CH3:8].[CH3:22][N:23]([CH3:35])[C:24]([C:26]1[N:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1)=[O:25].N#N.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][CH3:21])=[C:12]([C:29]2[CH:28]=[CH:27][C:26]([C:24]([N:23]([CH3:35])[CH3:22])=[O:25])=[N:31][CH:30]=2)[C:13]([C:14]#[N:15])=[C:16]([Cl:18])[CH:17]=1)(=[O:9])[CH3:8]

Participants

9

Reactant 5

HCID 947NitrogenHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 53438177[6-(Dimethylcarbamoyl)pyridin-3-yl]boronic acidHCID 866778184-Acetyl-2-bromo-6-chloro-3-methoxybenzonitrile

Product 1

HCID 866778195-(3-acetyl-5-chloro-6-cyano-2-methoxyphenyl)-N,N-dimethylpyridine-2-carboxamideYield 71%

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 (3.0 g, 20 mmol) in water (20 mL) was added to a mixture 4-acetyl-2-bromo-6-chloro-3-methoxybenzonitrile (2.5 g, 8.7 mmol) and {6-[(dimethylamino)carbonyl]pyridin-3-yl}boronic acid (1.9 g, 10.0 mmol, Example 301 Step 2) in acetonitrile (100 mL). The reaction was degassed with N2 and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (400 mg, 0.4 mmol) was added and the reaction mixture was degassed again with N2. The reaction was heated at 100° C. for 4 hrs and was complete by LC/MS. The reaction was allowed to cool to room temperature and was partitioned between water and EtOAc. The combined organic layer was washed with brine, dried over MgSO4, filtered, concentrated to give the crude product. The product was purified by FCC on silica gel eluting a hexane:ethyl acetate gradient to give 5-(3-acetyl-5-chloro-6-cyano-2-methoxyphenyl)-N,N-dimethylpyridine-2-carboxamide as yellow oil (2.2 g, 71%). LCMS calculated for C18H17ClN3O3(M+H)+: m/z=358.1; found: 358.1.

Workup

  1. additionwas added
  2. customthe reaction mixture was degassed again with N2
  3. temperatureto cool to room temperature
  4. customwas partitioned between water and EtOAc
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product
  10. customThe product was purified by FCC on silica gel eluting a hexane

Sources & evidence

ORD record
ord-da526135222849d3899d4a084056e555
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

Loading…