Potassium Carbonate → Tert-butyl[1-(5-chloro-4-cyano-3-{6-[(dimethylamino)carbonyl]pyridin-3-yl}-2-ethoxyphenyl)ethyl]carbamate

HRID 510979Notes

Reaction equation

HRID 510979 reaction equation
Br[C:2]1[C:3]([O:21][CH2:22][CH3:23])=[C:4]([CH:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:12])[CH:5]=[C:6]([Cl:10])[C:7]=1[C:8]#[N:9].[CH3:24][N:25]([CH3:37])[C:26]([C:28]1[N:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)=[O:27].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:10][C:6]1[C:7]([C:8]#[N:9])=[C:2]([C:31]2[CH:32]=[N:33][C:28]([C:26]([N:25]([CH3:37])[CH3:24])=[O:27])=[CH:29][CH:30]=2)[C:3]([O:21][CH2:22][CH3:23])=[C:4]([CH:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:12])[CH:5]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 53438177[6-(Dimethylcarbamoyl)pyridin-3-yl]boronic acidHCID 123418761Tert-butyl[1-(3-bromo-5-chloro-4-cyano-2-ethoxyphenyl)ethyl]carbamate

Product 1

HCID 88540918Tert-butyl[1-(5-chloro-4-cyano-3-{6-[(dimethylamino)carbonyl]pyridin-3-yl}-2-ethoxyphenyl)ethyl]carbamateYield 84.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

The tert-butyl [1-(3-bromo-5-chloro-4-cyano-2-ethoxyphenyl)ethyl]carbamate (0.05 g, 0.1 mmol, Example 179, peak 2) was combined with {6-[(dimethylamino)carbonyl]pyridin-3-yl}boronic acid (0.034 g, 0.17 mmol, Example 179, Step 5) in 1,4-dioxane (3.0 mL) and potassium carbonate (0.034 g, 0.25 mmol) dissolved in water (1.0 mL) in a tube. The reaction was degassed with nitrogen and the tetrakis(triphenylphosphine)palladium(0) (0.03 g, 0.02 mmol) was added and degassed again. The tube was sealed and heated in an oil bath to 90° C. After heating for 18 h the reaction was complete. This was allowed to cool to room temperature and partitioned between EtOAc and water. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to give the crude as a dark oil. The product was purified by chromatography on silica gel eluting with hexane:EtOAc gradient to give tert-butyl [1-(5-chloro-4-cyano-3-{6-[(dimethylamino)carbonyl]pyridin-3-yl}-2-ethoxyphenyl)ethyl]carbamate as a viscous oil (0.04 g, 66%). LCMS calculated for C24H30ClN4O4 (M+H)+: m/z=473.2. found: 473.1.

Workup

  1. customThe reaction was degassed with nitrogen
  2. customdegassed again
  3. customThe tube was sealed
  4. temperatureAfter heating for 18 h the reaction
  5. temperatureto cool to room temperature
  6. custompartitioned between EtOAc and water
  7. washThe organic layer was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customto give the crude as a dark oil
  11. customThe product was purified by chromatography on silica gel eluting with hexane

Sources & evidence

ORD record
ord-77bac3aa11eb45c599734e8a28d5b3a5
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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