Sodium Carbonate → 5-(4-Hydroxy-6-quinazolinyl)furan-2-carbaldehyde

HRID 1044724Notes

Reaction equation

HRID 1044724 reaction equation
C([O-])([O-])=O.[Na+].[Na+].I[C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][NH:12][C:11]2=[O:18].[CH:19]([C:21]1[O:25][C:24](B(O)O)=[CH:23][CH:22]=1)=[O:20]>CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[O:18]=[C:11]1[C:10]2[C:15](=[CH:16][CH:17]=[C:8]([C:24]3[O:25][C:21]([CH:19]=[O:20])=[CH:22][CH:23]=3)[CH:9]=2)[N:14]=[CH:13][NH:12]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343555-Formylfuran-2-boronic acidHCID 1354016666-Iodoquinazolin-4-one

Product 1

HCID 1361626165-(4-Hydroxy-6-quinazolinyl)furan-2-carbaldehydeYield 91.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
30 °C

Procedure

To a 40° C. solution of Na2CO3 (3.9 g, 36 mmol) in inert gas (nitrogen or argon) degassed aqueous dioxane (100 mL, 2:1 dioxane: H2O) was added [HP(t-Bu)3]BF4 (0.52 g, 1.8 mmol) and Pd(OAc)2 (0.4 g, 0.18 mmol). The mixture was stirred at 30° C. (internal temperature) under an atmosphere nitrogen for 30 min, and then 6-iodoquinazolin-4(3H)-one ((Va); 5 g, 18 mmol) and 5-formylfuran-2-ylboronic acid ((VIa); 4.1 g, 29 mmol) were added. The mixture was heated to 80° C. (internal temperature) and stirred until TLC analysis showed completion of the reaction. The reaction product mixture was cooled to ambient temperature and filtered through celite (1 g), and the filter cake was washed with n-BuOH (200 mL). The combined filtrates were separated and the organic layer was washed twice with a saturated aqueous solution of NaCl (100 mL each). The organic phase was concentrated down to about 50 mL under vacuum and the residue was cooled to ambient temperature with stirring to precipitate the product. The slurry was filtered and the filter cake was washed with n-BuOH (40 mL) and then dried at 60° C. under vacuum to give crude compound of formula (IX) (4.5 g, 91% HPLC, 16.5 mmol). 1H NMR (300 MHz, d6-DMSO, 1347-126-19): δ 7.47 (d, J=3.6 Hz, 1H), 7.68 (d, J=3.6 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 8.14 (d, J=2.1 Hz, 1H), 8.28 (dd, J=8.7 Hz, J=2.1 Hz, 1H), 8.53 (d, J=2.1 Hz, 1H), 9.64 (s, 1H).

Workup

  1. temperatureThe mixture was heated to 80° C. (internal temperature)
  2. stirringstirred until TLC analysis
  3. customcompletion of the reaction
  4. temperatureThe reaction product mixture was cooled to ambient temperature
  5. filtrationfiltered through celite (1 g)
  6. washthe filter cake was washed with n-BuOH (200 mL)
  7. customThe combined filtrates were separated
  8. washthe organic layer was washed twice with a saturated aqueous solution of NaCl (100 mL each)
  9. concentrationThe organic phase was concentrated down to about 50 mL under vacuum
  10. temperaturethe residue was cooled to ambient temperature
  11. stirringwith stirring
  12. customto precipitate the product
  13. filtrationThe slurry was filtered
  14. washthe filter cake was washed with n-BuOH (40 mL)
  15. customdried at 60° C. under vacuum

Sources & evidence

ORD record
ord-fc8ce1611e764c1b801c23f7f7842d68
Source dataset
uspto-grants-2013_10
Patent number
US08563719B2

Reaction notes

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