Toluene → 2-(4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl)-N-(5-phenylpyridin-2-yl)acetamide

HRID 1036181

Reaction equation

HRID 1036181 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][N:13]=2)=[O:10])=[CH:4][C:3]=1[C:24]([F:27])([F:26])[F:25].[CH3:28][C:29]1[CH:34]=[C:33](B(O)O)[CH:32]=[CH:31][N:30]=1.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>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(O)C>[CH3:28][C:29]1[CH:34]=[C:33]([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:14][N:13]=3)=[O:10])=[CH:4][C:3]=2[C:24]([F:27])([F:26])[F:25])[CH:32]=[CH:31][N:30]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 41926642-Methylpyridine-4-boronic acidHCID 682471662-(4-bromo-3-(trifluoromethyl)phenyl)-N-(5-phenylpyridin-2-yl)acetamide

Product 1

HCID 584478172-(4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl)-N-(5-phenylpyridin-2-yl)acetamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a sealed tube were added 2-(4-bromo-3-(trifluoromethyl)phenyl)-N-(5-phenylpyridin-2-yl)acetamide 46-7 (73 mg, 0.17 mmol), 2-methylpyridin-4-ylboronic acid (35 mg, 0.255 mmol), Pd(PPh3)4 (12 mg, 0.017 mmol), toluene (0.8 mL), ethanol (0.2 mL) and 2M Na2CO3 (0.5 mL). The reaction mixture was bubbled with nitrogen for 2 minutes and stirred at 90° C. for 10 hours. After cooled down to room temperature, the reaction mixture was diluted with ethyl acetate (50 mL) and washed with saturated NaHCO3 aqueous solution and brine. The organic phase was dried over Na2SO4 and concentrated to dryness by rotary evaporation. The crude product was purified by reverse phase HPLC to give 2-(4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl)-N-(5-phenylpyridin-2-yl)acetamide 46 as white solid. MS m/z 448.1 (M+1); 1H NMR 400 MHz (CDCl3) δ 8.48-8.45 (m, 2H), 8.28 (d, 1H, J=8.4 Hz), 7.92 (dd, 1H, J1=8.4 Hz, J2=2.4 Hz), 7.75 (s, 1H), 7.61 (dd, 1H, J1=8.0 Hz, J2=1.2 Hz), 7.54-7.52 (m, 2H), 7.47-7.43 (m, 2H), 7.39-7.37 (m, 1H), 7.28 (d, 1H, J=7.6 Hz), 7.14 (s, 1H), 7.10 (d, 1H, J=5.2 Hz), 3.86 (s, 2H), 2.59 (s, 3H).

Workup

  1. customThe reaction mixture was bubbled with nitrogen for 2 minutes
  2. temperatureAfter cooled down to room temperature
  3. additionthe reaction mixture was diluted with ethyl acetate (50 mL)
  4. washwashed with saturated NaHCO3 aqueous solution and brine
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated to dryness by rotary evaporation
  7. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-b472fb107b62469a9fcd94ff1d614833
Source dataset
uspto-grants-2013_10
Patent number
US08546396B2

Linked notes

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