Ethyl Acetate → HCID 67329881, compound

HRID 1677633Notes

Reaction equation

HRID 1677633 reaction equation
[C:1]([C:3]1[C:4]([NH:10][N:11]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[N:5][CH:6]=[CH:7][C:8]=1I)#[N:2].[F:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][C:28]=1[NH:37][C:38]([NH:40][C:41]1[CH:46]=[CH:45][C:44](B2OC(C)(C)C(C)(C)O2)=[CH:43][CH:42]=1)=[O:39].C([O-])(O)=O.[Na+].C(OCC)(=O)C>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>[C:1]([C:3]1[C:4]([NH:10][N:11]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[N:5][CH:6]=[CH:7][C:8]=1[C:44]1[CH:43]=[CH:42][C:41]([NH:40][C:38]([NH:37][C:28]2[CH:29]=[C:30]([C:33]([F:34])([F:36])[F:35])[CH:31]=[CH:32][C:27]=2[F:26])=[O:39])=[CH:46][CH:45]=1)#[N:2]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 161252301-(2-Fluoro-5-(trifluoromethyl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 67329719HCID 67329719, compound

Product 1

HCID 67329881HCID 67329881, compoundYield 75.6%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a solution of 110 mg of di-tert-butyl (3-cyano-4-iodopyrid-2-yl)-hydrazinedicarboxylate and 122 mg of 1-(2-fluoro-5-trifluoromethylphenyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea in 5.5 mL of dioxane are added 57 mg of NaHCO3 in 1.7 mL of water. 26 mg of tetrakis(triphenylphosphine)palladium are then added and the reaction is refluxed at 100° C. After 2 hours 30 minutes, the pale yellow solution is cooled to 20° C. and 10 mL of ethyl acetate are added. The organic phase is washed twice with 8 mL of water and then with 8 mL of brine. After drying over magnesium sulfate and concentrating under reduced pressure, the residual yellow oil is purified on a prepacked Biotage KP-Sil column of 60 Å SiO2 32-63 μm (9/1 cyclohexane/ethyl acetate). 114 mg of di-tert-butyl (3-cyano-4-{4-[3-(2-fluoro-5-trifluoromethylphenyl)ureido]phenyl}pyrid-2-yl)hydrazinedicarboxylate are obtained.

Workup

  1. temperaturethe pale yellow solution is cooled to 20° C.
  2. washThe organic phase is washed twice with 8 mL of water
  3. dry with materialAfter drying over magnesium sulfate
  4. concentrationconcentrating under reduced pressure
  5. customthe residual yellow oil is purified on a prepacked Biotage KP-Sil column of 60 Å SiO2 32-63 μm (9/1 cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-46da0a71b40b47c592c0e8f84dddb26f
Source dataset
uspto-grants-2011_08
Patent number
US08008322B2

Reaction notes

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