Sodium Carbonate → HCID 178425211, compound

HRID 1500983Notes

Reaction equation

HRID 1500983 reaction equation
Br[C:2]1[C:3]([C:29]#[N:30])=[C:4]([CH:26]=[CH:27][CH:28]=1)[O:5][C:6]1[CH:24]=[CH:23][C:9]([C:10]([NH:12][CH2:13][C:14]2[C:15]([OH:22])=[N:16][C:17]([CH3:21])=[CH:18][C:19]=2[CH3:20])=[O:11])=[CH:8][C:7]=1[Cl:25].[N:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+]>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:25][C:7]1[CH:8]=[C:9]([CH:23]=[CH:24][C:6]=1[O:5][C:4]1[CH:26]=[CH:27][CH:28]=[C:2]([C:34]2[CH:35]=[CH:36][N:31]=[CH:32][CH:33]=2)[C:3]=1[C:29]#[N:30])[C:10]([NH:12][CH2:13][C:14]1[C:15]([OH:22])=[N:16][C:17]([CH3:21])=[CH:18][C:19]=1[CH3:20])=[O:11]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 178425202HCID 178425202, compound

Product 1

HCID 178425211HCID 178425211, compoundYield 70%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

To a solution of 4-(3-bromo-2-cyanophenoxy)-3-chloro-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide (500 mg, 1.03 mmol), pyridin-4-ylboronic acid (150 mg, 1.2 mmol), sodium carbonate (425 mg, 3.07 mmol) in 1,4-dioxane (20 mL) and water (5 mL) was added tetrakis(triphenylphosphine)palladium(0) (118 mg, 0.1 mmol). The reaction mixture was stirred at 90° C. under nitrogen atmosphere for 12 hours. After the reaction, it was allowed to cool to room temperature, and concentrated in vacuo, then diluted with ethyl acetate, washed with water. The organic phase was dried over anhydrous sodium sulfate. The mixture was filtered and the filtrate was concentrated. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to give the pure product 3-chloro-4-(2-cyano-3-(pyridin-4-yl)phenoxy)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide (348 mg, 70%). LRMS (M+H+) m/z: calcd 484.13. found 484. 1H NMR (300 MHz, d6-DMSO): δ 11.48 (s, 1H), 8.75 (d, J=6.0 Hz, 2H), 8.55 (t, J=4.5 Hz, 1H), 8.15 (s, 1H), 7.94-7.91 (m, 1H), 7.76 (t, J=7.8 Hz, 1H), 7.67-7.65 (m, 2H), 7.44 (d, J=7.5 Hz, 1H), 7.39 (d, J=8.4 Hz, 1H), 7.01 (d, J=8.4 Hz, 1H), 5.86 (s, 1H), 4.29 (d, J=4.8 Hz, 2H), 2.16 (s, 3H), 2.11 (s, 3H).

Workup

  1. customAfter the reaction, it
  2. temperatureto cool to room temperature
  3. concentrationconcentrated in vacuo
  4. additiondiluted with ethyl acetate
  5. washwashed with water
  6. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  7. filtrationThe mixture was filtered
  8. concentrationthe filtrate was concentrated
  9. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-7e09e0de7d8346a78427e93cedee81c7
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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