Sodium Carbonate → HCID 178425213, compound

HRID 1500982Notes

Reaction equation

HRID 1500982 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].C(OC([N:38]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[N:39]1)=O)(C)(C)C.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:41]2[CH:42]=[N:38][NH:39][CH:40]=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 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 178425202HCID 178425202, compound

Product 1

HCID 178425213HCID 178425213, compoundYield 68%

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), tert-butyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (323 mg, 1.1 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-(1H-pyrazol-4-yl)phenoxy)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide (331 mg, 68%). LRMS (M+H+) m/z: calcd 473.13. found 473. 1H NMR (300 MHz, d6-DMSO): δ 13.33 (s, 1H), 11.48 (s, 1H), 8.53 (t, J=4.8 Hz, 1H), 8.35 (s, 1H), 8.15 (s, 1H), 8.07 (s, 1H), 7.90 (d, J=6.9 Hz, 1H), 7.61 (t, J=8.1 Hz, 1H), 7.51 (d, J=7.8 Hz, 1H), 7.32 (d, J=8.4 Hz, 1H), 6.74 (d, J=8.1 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-f1f9cc5e7946417da519f75e5de7643b
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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