Potassium Carbonate → HCID 46841561, compound

HRID 1846341Notes

Reaction equation

HRID 1846341 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]2[C:19]2[CH:20]=[N:21][C:22](Cl)=[CH:23][CH:24]=2)=[CH:4][CH:3]=1.[CH3:26]B1OB(C)OB(C)O1.C([O-])([O-])=O.[K+].[K+]>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>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]2[C:19]2[CH:20]=[N:21][C:22]([CH3:26])=[CH:23][CH:24]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 574072Trimethylboroxine2×HCID 46841411HCID 46841411, compound

Product 1

HCID 46841561HCID 46841561, compoundYield 13.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

3-(4-chlorophenyl)-2-(6-chloropyridin-3-yl)quinazolin-4(3H)-one (0.200 g, 0.54 mmol), trimethyboroxine (0.076 mL, 0.54 mmol), Pd(PPh3)4 (0.063 g, 0.05 mmol), and K2CO3 (0.224 g, 1.62 mmol) were combined in dioxane (10 mL) and heated at reflux under nitrogen for 5 hours. Additional Pd(PPh3)4 (50 mg) and trimethylboroxine (0.200 mL) were added and reflux was continued for 28 hours. The reaction mixture was cooled to room temperature, filtered through Celite®, with THF washings, concentrated, and purified by flash chromatography on silica gel, eluting with 40% ethyl acetate/heptane to 100% ethyl acetate. Further purification by reverse-phase HPLC, eluting with 10% to 90% CH3CN in water with 0.1% TFA, afforded the title compound as a white solid (0.025 g, 13%). 1H-NMR (300 MHz, DMSO-6): δ 8.46 (d, J=2.0 Hz, 1H), 8.21 (d, J=7.0 Hz, 1H), 7.90-7.95 (m, 1H), 7.79 (d, J=7.9 Hz, 1H), 7.60-7.65 (m, 2H), 7.42-7.46 (m, 4H), 7.16 (d, J=8.1 Hz, 1H), 2.41 (s, 3H). MS (APCI) m/z: 348 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureat reflux under nitrogen for 5 hours
  3. temperaturereflux
  4. filtrationfiltered through Celite®, with THF washings
  5. concentrationconcentrated
  6. custompurified by flash chromatography on silica gel
  7. washeluting with 40% ethyl acetate/heptane to 100% ethyl acetate
  8. customFurther purification by reverse-phase HPLC
  9. washeluting with 10% to 90% CH3CN in water with 0.1% TFA

Sources & evidence

ORD record
ord-be6beaffe8574e7fa93c976062ad82cf
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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