Benzaldehyde → HCID 11709006, compound

HRID 426372Notes

Reaction equation

HRID 426372 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]#[N:9])[C:5]([C:10]#[N:11])=[CH:4][C:3]=1[NH2:12].[CH:13](=O)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O=O.[CH2:23]1[CH2:33]CN2C(=NCCC2)C[CH2:24]1.ICCC>CN1C(=O)CCC1.C(OCC)(=O)C>[C:10]([C:5]1[C:6]([C:8]#[N:9])=[CH:7][C:2]2[N:1]([CH2:24][CH2:23][CH3:33])[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:12][C:3]=2[CH:4]=1)#[N:11]

Participants

8

Reactant 5

HCID 240BenzaldehydeHCID 977OxygenHCID 336431-Iodopropane2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 6763684,5-Diaminophthalonitrile

Product 1

HCID 11709006HCID 11709006, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
120 °C

Procedure

A 25 mL round-bottom flask was charged with 3 (316 mg, 2.00 mmol), NMP (10 mL), benzaldehyde, (202 μL, 2.00 mmol), and a magnetic stirring bar. The flask was fitted with a Hickman still, placed in an oil bath heated to 120° C., and stirred for 1 h. Then FeCl3.6H2O (27 mg, 0.10 mmol) was added to the reaction vessel and oxygen was bubbled through the mixture as it was heated and stirred for an additional 20 h. The reaction mixture was then removed from heat and added to ethyl acetate. The ethyl acetate solution was washed three times with water, then washed with brine, dried over Na2SO4, filtered, and concentrated to dryness. The residue (458 mg, 1.88 mmol) was dissolved in NMP (2 mL) and heated to 80° C. Then DBU (280 μL, 1.88 mmol) was added and the mixture was stirred for 2 min, and iodopropane (183 μL, 1.88 mmol) was added. After 20 min, the mixture was treated with a second round of DBU and iodopropane, and after an additional 20 min, a third round of reagents was added. After a final 20 min of heating, the mixture was transferred to ethyl acetate and washed three times with water, followed by brine. After drying the organic layer over Na2SO4, the mixture was filtered, concentrated to dryness, and chromatographed (silica, CH2Cl2, 3% ethyl acetate, 1% isopropanol), yielding an off-white solid (253 mg, 44%): mp 183-185° C.; 1H NMR (CDCl3) δ 0.90 (t, J=7.6 Hz, 2H), 1.81-1.92 (m, 2H), 4.29 (t, J=7.6 Hz, 2H), 7.56-7.62 (m, 3H), 7.70-7.73 (m, 2H), 7.89 (s, 1H), 8.20 (s, 1H); 13C NMR (CDCl3) δ 11.4, 23.5, 47.3, 108.7, 109.0, 116.7, 116.8, 116.9, 126.6, 128.8, 129.5, 129.5, 131.4, 137.8, 145.4, 159.5; FAB-MS obsd 287.1302, calcd 287.1297 [(M+H)+; M=C18H14N4].

Workup

  1. customThe flask was fitted with a Hickman still
  2. customplaced in an oil bath
  3. customwas bubbled through the mixture as it
  4. temperaturewas heated
  5. stirringstirred for an additional 20 h
  6. customThe reaction mixture was then removed
  7. temperaturefrom heat
  8. additionadded to ethyl acetate
  9. washThe ethyl acetate solution was washed three times with water
  10. washwashed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated to dryness
  14. temperatureheated to 80° C
  15. stirringthe mixture was stirred for 2 min
  16. waitAfter 20 min
  17. waitafter an additional 20 min
  18. additiona third round of reagents was added
  19. temperatureAfter a final 20 min of heating
  20. washwashed three times with water
  21. dry with materialAfter drying the organic layer over Na2SO4
  22. filtrationthe mixture was filtered
  23. concentrationconcentrated to dryness
  24. customchromatographed (silica, CH2Cl2, 3% ethyl acetate, 1% isopropanol)

Sources & evidence

ORD record
ord-1eae74196bfa497893d9048ee912e679
Source dataset
uspto-grants-2012_01
Patent number
US08106393B2

Reaction notes

Loading…