Sodium Carbonate → 6-(3-Butyl-5-methyl-isoxazol-4-ylmethoxy)-pyridazine-3-carboxylic acid methyl ester

HRID 1958068Notes

Reaction equation

HRID 1958068 reaction equation
[CH2:1]([C:5]1[C:9]([CH2:10][O:11][C:12]2[N:13]=[N:14][C:15](Cl)=[CH:16][CH:17]=2)=[C:8]([CH3:19])[O:7][N:6]=1)[CH2:2][CH2:3][CH3:4].C(C1C([CH2:29][O:30][C:31]2N=NC(I)=CC=2)=C(C)ON=1)CCC.C(=O)([O-])[O-:40].[Na+].[Na+]>CO.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:31][O:30][C:29]([C:15]1[N:14]=[N:13][C:12]([O:11][CH2:10][C:9]2[C:5]([CH2:1][CH2:2][CH2:3][CH3:4])=[N:6][O:7][C:8]=2[CH3:19])=[CH:17][CH:16]=1)=[O:40]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 86647344HCID 86647344, compoundHCID 86647345HCID 86647345, compound

Product 1

HCID 666438716-(3-Butyl-5-methyl-isoxazol-4-ylmethoxy)-pyridazine-3-carboxylic acid methyl esterYield 36%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of 3-(3-butyl-5-methyl-isoxazol-4-ylmethoxy)-6-chloro-pyridazine and 3-(3-butyl-5-methyl-isoxazol-4-ylmethoxy)-6-iodo-pyridazine (˜1:3 mixture, 2.6 g, ˜7.0 mmol) and sodium carbonate (738 mg, 7.0 mmol) in methanol (20 mL) was evacuated and filled with argon five times. 1,1′-Bis(diphenylphosphino)ferrocene (386 mg, 0.7 mmol) and palladium(II) acetate (156 mg, 0.7 mmol) were added then the flask was evacuated again and filled with carbon monoxide. The reaction mixture was then heated to 50° C. After 15 h the reaction mixture was cooled, filtered through decalite and evaporated. The residue was purified by chromatography (silica, 0 to 50% ethyl acetate in heptane) to give the title compound (760 mg, ˜36%) as an orange solid. MS: m/e=306.1 [M+H]+.

Workup

  1. customwas evacuated
  2. additionfilled with argon five times
  3. customthe flask was evacuated again
  4. additionfilled with carbon monoxide
  5. temperatureAfter 15 h the reaction mixture was cooled
  6. filtrationfiltered through decalite
  7. customevaporated
  8. customThe residue was purified by chromatography (silica, 0 to 50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-d4a30fb09bb042f398f2abb73ac628ab
Source dataset
uspto-grants-2013_04
Patent number
US08410104B2

Reaction notes

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