4-Methoxybenzaldehyde → HCID 62483451, compound

HRID 1504500Notes

Reaction equation

HRID 1504500 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH2:7])[N:2]=1.[CH3:8][O:9][C:10]1[CH:17]=[CH:16][C:13]([CH:14]=O)=[CH:12][CH:11]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti](Cl)(Cl)(Cl)Cl>[CH3:8][O:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14][NH:7][C:3]2[N:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[CH:12][CH:11]=1

Participants

6

Reactant 3

HCID 312444-MethoxybenzaldehydeHCID 230373AminopyridazineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 62483451HCID 62483451, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 131734328HCID 131734328, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of pyridazin-3-ylamine (105 g, 1.1 mol, 1 eq) and 4-methoxybenzaldehyde (150 g, 1.1 mol, 1 eq) in DCM (3 L), was added titanium(IV) chloride triisopropoxide (572 g, 2.2 mol, 2 eq). The reaction mixture was stirred at RT for 8 h. The reaction mixture was cooled to 0° C. and sodium triacetoxyborohydride (933 g, 4.4 mol, 4 eq) was added. The reaction mixture was allowed to stir at RT 5 h. After completion of the reaction, the reaction mixture was cooled to 0° C., quenched with ice water and the solid was filtered through celite pad. The layers were separated and the aqueous layer extracted with DCM (1 L). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude mass was dissolved in minimum amount of DCM and the product was extracted in 1.5 N HCl thrice. The aqueous layer was basified with saturated NaHCO3 solution; the precipitated product was filtered and dried. Then the solid obtained was washed with minimum amount of diethyl ether and dried to get 60 g of the title compound as pale pink solid (0.27 mol, 25% yield). MS (ESI pos. ion) riVz: (M+2)+=216.7. 1H NMR (400 MHz, Chloroform-d) δ 8.56 (dd, J=1.20, 4.60 Hz, 1H), 7.31 (dd, J=2.80, 11.60 Hz, 2H), 7.15 (dd, J=4.40, 9.00 Hz, 1H), 6.89 (dd, J=2.80, 5.80 Hz, 2H), 6.63 (dd, J=1.20, 9.20 Hz, 1H), 5.15 (br. s, 1H), 4.55 (d, J=5.60 Hz, 2H), 3.81 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringto stir at RT 5 h
  3. customAfter completion of the reaction
  4. temperaturethe reaction mixture was cooled to 0° C.
  5. customquenched with ice water
  6. filtrationthe solid was filtered through celite pad
  7. customThe layers were separated
  8. extractionthe aqueous layer extracted with DCM (1 L)
  9. dry with materialThe combined organic layer was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe crude mass was dissolved in minimum amount of DCM
  13. extractionthe product was extracted in 1.5 N HCl thrice
  14. filtrationthe precipitated product was filtered
  15. customdried
  16. customThen the solid obtained
  17. washwas washed with minimum amount of diethyl ether
  18. customdried

Sources & evidence

ORD record
ord-45cd5ba2b6d34c0e9fc753791ef8b232
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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