Toluene → N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl)acetamide

HRID 592192Notes

Reaction equation

HRID 592192 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:30])[CH2:18][C:19]3[CH:24]=[CH:23][C:22](Br)=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:31][C:32]1[CH:37]=[C:36](B(O)O)[CH:35]=[CH:34][N:33]=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>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:30])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:36]4[CH:35]=[CH:34][N:33]=[C:32]([CH3:31])[CH:37]=4)=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 41926642-Methylpyridine-4-boronic acidHCID 58447760N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-bromo-3-(trifluoromethyl)phenyl)acetamide

Product 1

HCID 58447713N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl)acetamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

To a reaction vessel charged with N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-bromo-3-(trifluoromethyl)phenyl)acetamide 192-1 (300 mg, 0.62 mmol), 2-methylpyridin-4-ylboronic acid 172-1 (127 mg, 0.93 mmol) and Pd(PPh3)4 (36 m g, 0.03 mmol) was added toluene (6 mL), ethanol (2 mL) and saturated sodium carbonate (2 mL). The reaction mixture was flushed with nitrogen and heated to 110° C. for 10 hours. After the reaction was cooled down to room temperature, it was partitioned between ethyl acetate and saturated NaHCO3 and the organic phase was washed with brine and dried over Na2SO4. The solvent was removed by rotary evaporation and the residue was purified by reverse phase HPLC to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl)acetamide 172. MS m/z 498.2 (M+1). 1H NMR 400 MHz (DMSO-d6) δ10.67 (s, 1H), 8.66 (d, 1H), 8.05 (m, 1H), 7.94 (m, 2H), 7.75 (d, 1H), 7.52 (s, 1H), 7.45 (m, 3H), 3.88 (s, 2H), 3.58 (b, 4H), 3.14 (b, 2H), 3.09 (b, 2H), 2.61 (s, 3H), 2.05 (s, 3H).

Workup

  1. customThe reaction mixture was flushed with nitrogen
  2. temperatureAfter the reaction was cooled down to room temperature
  3. customit was partitioned between ethyl acetate and saturated NaHCO3
  4. washthe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed by rotary evaporation
  7. customthe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-fd9b9e67654947bc99d04b171739a3ed
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Reaction notes

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