Dimethyl Sulfoxide → 5-(4-Hydroxy-6-quinazolinyl)furan-2-carbaldehyde

HRID 2370675Notes

Reaction equation

HRID 2370675 reaction equation
CS(C)=O.[CH:5]([C:7]1[O:11][C:10](B(O)O)=[CH:9][CH:8]=1)=[O:6].C([O-])(=O)C.[K+].I[C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N:27]=[CH:26][NH:25][C:24]2=[O:31]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[O:31]=[C:24]1[C:23]2[C:28](=[CH:29][CH:30]=[C:21]([C:10]3[O:11][C:7]([CH:5]=[O:6])=[CH:8][CH:9]=3)[CH:22]=2)[N:27]=[CH:26][NH:25]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 517044Potassium AcetateHCID 27343555-Formylfuran-2-boronic acidHCID 1354016666-Iodoquinazolin-4-one

Product 1

HCID 1361626165-(4-Hydroxy-6-quinazolinyl)furan-2-carbaldehydeYield 98%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Procedure

A 5:2 v/v solvate mixture of Dimethyl sulfoxide (DMSO) and H2O (1400 mL) was degassed for 30 min at ambient temperature using nitrogen. Under an atmosphere of nitrogen, 5-formylfuran-2-ylboronic acid ((VIa); 26.8 g, 193 mmol) was added into this mixture and dissolved. [HP(t-Bu)3]BF4 (840 mg, 2.94 mmol) and palladium acetate (Pd(OAc)2, 680 mg, 2.94 mmol) was added and the mixture was stirred at ambient temperature for 20 min. Then, potassium acetate (AcOK, 18.8 g, 192 mmol) was added into the reactor and was stirred for 20 min. 6-Iodoquinazolin-4(3H)-one ((Va); 40 g, 147 mmol) was added. Then the reaction mixture was heated to 80±5° C. (internal temperature). Upon completion of the reaction (HPLC), the reaction mixture was hot-filtered, then hot water (400 mL, 80±5° C.) was added into the filtrate. This was slowly cooled to 0-15° C. (solid started to precipitate at 70° C. (internal temperature)) and was then filtered. The filter cake was washed with H2O (80 mL), then with MeCN (60 mL), and dried in vacuo at 60±5° C. for 6 h to provide 5-(4-oxo-3,4-dihydroquinazolin-6-yl)-furan-2-carbaldehyde ((IX); 34.6 g, 144 mmol) with 99.7% HPLC purity in 97.6% HPLC yield. 1H NMR (300 MHz, d6-DMSO): δ 7.47 (d, J=3.8 Hz, 1H), 7.69 (d, J=3.8 Hz, 1H), 7.77 (d, J =8.6 Hz, 1H), 8.17 (s, 1H), 8.27 (dd, J=8.6, 2.1 Hz, 1H), 8.52 (d, J=2.1 Hz, 1H), 9.66 (s, 1H); 13C NMR (75 MHz, CDCl3): δ 110.5, 122.6, 123.9, 126.0, 127.5, 129.0, 131.4, 147.1, 150.1, 152.7, 157.6, 161.2, 178.8; ESI-MS, Pos: [M+H]+m/z 241; IR (cm−1): 1713, 1671, 1604, 1462; m.p.: 267° C.

Workup

  1. customwas degassed for 30 min at ambient temperature
  2. dissolutiondissolved
  3. stirringwas stirred for 20 min
  4. temperatureThen the reaction mixture was heated to 80±5° C. (internal temperature)
  5. customUpon completion of the reaction (HPLC)
  6. filtrationthe reaction mixture was hot-filtered
  7. additionhot water (400 mL, 80±5° C.) was added into the filtrate
  8. temperatureThis was slowly cooled to 0-15° C.
  9. custom(solid started to precipitate at 70° C. (internal temperature))
  10. filtrationwas then filtered
  11. washThe filter cake was washed with H2O (80 mL)
  12. dry with materialwith MeCN (60 mL), and dried in vacuo at 60±5° C. for 6 h

Sources & evidence

ORD record
ord-e65e36f228d44691b0a76f96275ec4e9
Source dataset
uspto-grants-2014_04
Patent number
US08710221B2

Reaction notes

Loading…