Sodium Carbonate → HCID 178425204, compound

HRID 1500985Notes

Reaction equation

HRID 1500985 reaction equation
Br[C:2]1[CH:28]=[CH:27][CH:26]=[CH:25][C:3]=1[O:4][C:5]1[CH:23]=[CH:22][C:8]([C:9]([NH:11][CH2:12][C:13]2[C:14]([OH:21])=[N:15][C:16]([CH3:20])=[CH:17][C:18]=2[CH3:19])=[O:10])=[CH:7][C:6]=1[Cl:24].[N:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>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.O>[Cl:24][C:6]1[CH:7]=[C:8]([CH:22]=[CH:23][C:5]=1[O:4][C:3]1[CH:25]=[CH:26][CH:27]=[CH:28][C:2]=1[C:32]1[CH:33]=[CH:34][N:29]=[CH:30][CH:31]=1)[C:9]([NH:11][CH2:12][C:13]1[C:14]([OH:21])=[N:15][C:16]([CH3:20])=[CH:17][C:18]=1[CH3:19])=[O:10]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2734379(Pyridin-4-yl)boronic acidHCID 178425203HCID 178425203, compound

Product 1

HCID 178425204HCID 178425204, compoundYield 32.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

4-(2-Bromophenoxy)-3-chloro-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide (90 mg, 0.2 mmol), pyridin-4-ylboronic acid (48 mg, 0.4 mmol), tetrakis(triphenylphosphine)palladium (45 mg, 0.04 mmol), sodium carbonate (62 mg, 0.6 mmol), dioxane (8 mL) and water (2 mL) were added to a flask. The mixture was stirred at 90° C. for 12 hours under nitrogen atmosphere. The resultant mixture was concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to give 3-chloro-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-(2-(pyridin-4-yl)phenoxy)benzamide as a light yellow solid (30 mg, 32%). LRMS (M+H+) m/z: calcd 459.13. found 459. HPLC purity (214 nm): 98%. 1H NMR (300 MHz, d6-DMSO): δ 11.46 (s, 1H), 8.57 (d, J=6.3 Hz, 2H), 8.40 (t, J=4.5 Hz, 1H), 8.02 (d, J=1.8 Hz, 1H), 7.73 (dd, J=8.7 Hz, J=2.1 Hz, 1H), 7.62-7.46 (m, 4H), 7.36 (t, J=6.3 Hz, 1H), 7.16 (d, J=2.1 Hz, 1H), 6.78 (d, J=6.3 Hz, 1H), 5.84 (s, 1H), 4.24 (d, J=4.5 Hz, 2H), 2.15 (s, 3H), 2.10 (s, 3H).

Workup

  1. concentrationThe resultant mixture was concentrated
  2. customto give a residue
  3. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-b1372abc5da14fe6a19dfd25c540e307
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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