Potassium Carbonate → HCID 59026840, compound

HRID 658395Notes

Reaction equation

HRID 658395 reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]1[C:9]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])=[CH:8][N:7]=[CH:6][C:5]=1Br.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>[CH3:1][O:2][C:3](=[O:19])[C:4]1[C:9]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])=[CH:8][N:7]=[CH:6][C:5]=1[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[Cl:20]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27343222-Chlorophenylboronic acidHCID 59026790HCID 59026790, compound

Product 1

HCID 59026840HCID 59026840, compoundYield 80.1%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

3-Bromo-5-(2-fluoro-phenylamino)-isonicotinic acid methyl ester (250 mg, 0.77 mmol), 2-chlorophenylboronic acid (0.18 g, 1.2 mmol), Pd(OAc)2 (10 mg, 0.025 mmol), S-Phos (20 mg, 0.05 mmol), and K2CO3 (0.32 g, 2.3 mmol) were suspended in dioxane/H2O (1.65 mL, 9/1, v/v) and stirred overnight at 100° C. The reaction solution was diluted with EtOAc, and filtered through an Extrelut column. The column was washed with EtOAc, and the filtrate was concentrated. The crude product was purified via Biotage eluting with a gradient of 0 to 50% EtOAc in hexanes to afford the desired product (220 mg, 80%) as a yellow oil. LC-MS (M+H=357, obsd.=357).

Workup

  1. filtrationfiltered through an Extrelut column
  2. washThe column was washed with EtOAc
  3. concentrationthe filtrate was concentrated
  4. customThe crude product was purified via Biotage
  5. washeluting with a gradient of 0 to 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-93cb717c36c34a87baf2a071ecbb5849
Source dataset
uspto-grants-2011_12
Patent number
US08076486B2

Reaction notes

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