Acrolein → 3-[2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]propionaldehyde

HRID 1266978Notes

Reaction equation

HRID 1266978 reaction equation
[CH:1]1[CH:6]=[C:5]2[C:7]([NH:9][C:10]([NH:12][C:4]2=[CH:3][CH:2]=1)=[O:11])=[O:8].[CH:13]([CH:15]=[CH2:16])=[O:14]>CO.C(OCC)(=O)C.O>[O:11]=[C:10]1[N:9]([CH2:16][CH2:15][CH:13]=[O:14])[C:7](=[O:8])[C:5]2[C:4](=[CH:3][CH:2]=[CH:1][CH:6]=2)[NH:12]1

Participants

6

Reactant 2

HCID 7847AcroleinHCID 64048Quinazolinedione

Product 1

HCID 185451873-[2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]propionaldehydeYield 59.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent3×HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

Benzoylene urea (4.0 9, 24.7 mmol), Triton B (40 wt % in methanol) (11.0 mL, 24.7 mmol), water (80 mL) and methanol (400 mL) were combined at ambient temperature and stirred vigorously for 15 minutes. (until all the solids had gone into solution). To this colorless solution, acrolein (1.7 mL, 24.7 mmol) in methanol (20 mL) was added dropwise over 5 minutes. to give a yellow solution. The reaction was then heated to 55° C. and stirred for 2 hours. and then at room temperature for approximately 16 hours. The yellow solution was concentrated to give a yellow oil which was taken up in ethyl acetate (25 mL) and water (50 mL). The aqueous layer was extracted again with ethyl acetate (25 mL). The organic layers were combined, washed with 1N HCl (20 mL), water (20 mL), saturated sodium bicarbonate solution (20 mL) and brine (20 mL), the organic layer was dried over magnesium sulfate and concentrated to give 3-[2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]propionaldehyde as a yellow foam (3.2 g, 59%) which was used without further purification. The NMR data showed a purity of ˜70%. NMR CDCl3 δ9.85 (s, 1H), 8.10-8.06 (m, 1H), 7.63-7.57 (m, 1H), 7.24-7.19 (m, 1H), 7.13-7.07 (m, 1H), 4.44-4.40 (m, 2H), 2.85 (dt, 2H, J1,2=2 Hz, J1,3=7 Hz); MS=219 (p+1).

Workup

  1. customwere combined at ambient temperature
  2. customto give a yellow solution
  3. stirringstirred for 2 hours
  4. waitand then at room temperature for approximately 16 hours
  5. concentrationThe yellow solution was concentrated
  6. customto give a yellow oil which
  7. extractionThe aqueous layer was extracted again with ethyl acetate (25 mL)
  8. washwashed with 1N HCl (20 mL), water (20 mL), saturated sodium bicarbonate solution (20 mL) and brine (20 mL)
  9. dry with materialthe organic layer was dried over magnesium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-073276b0e1bb40b8abeee2d365ecd3f8
Source dataset
uspto-grants-2003_04
Patent number
US06552015B2

Reaction notes

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