5-Iodo-2-(trifluoromethyl)pyridine → 3,4-Bis(benzyloxy)-6-{[6-(trifluoromethyl)pyridin-3-yl]ethynyl}pyridazine

HRID 927064Notes

Reaction equation

HRID 927064 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][CH:7]=1.N1(C2CCCCCCCCCC2)CCCN=CCCCCC1.[CH2:34]([O:41][C:42]1[N:43]=[N:44][C:45]([C:56]#[CH:57])=[CH:46][C:47]=1[O:48][CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[CH2:34]([O:41][C:42]1[N:43]=[N:44][C:45]([C:56]#[C:57][C:2]2[CH:7]=[N:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)=[CH:46][C:47]=1[O:48][CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

7

Reactant 3

HCID 455981185-Iodo-2-(trifluoromethyl)pyridineHCID 866770253,4-Bis(benzyloxy)-6-ethynylpyridazine2×HCID 1296629601,8-Diazabicycloundec-7ene

Product 1

HCID 712701343,4-Bis(benzyloxy)-6-{[6-(trifluoromethyl)pyridin-3-yl]ethynyl}pyridazineYield 10%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A microwave vial was charged with 5-iodo-2-(trifluoromethyl)pyridine (617 mg, 2.260 mmol), copper(I) iodide (39.1 mg, 0.205 mmol), bis(triphenylphosphine)palladium(II) chloride (72.1 mg, 0.103 mmol), 1,8-diazabicycloundec-7-ene (DBU; 1858 μl, 12.33 mmol) and tetrahydrofuran (6849 μl). The reaction mixture was then purged and evacuated with nitrogen and to this was then added 3,4-bis(benzyloxy)-6-ethynylpyridazine (Intermediate 5: 650 mg, 2.1 mmol). The reaction was heated to 80° C. whilst being subjected to microwave radiation for 1 hour. Upon cooling the reaction mixture was partitioned between ethyl acetate and water, at which point a solid formed which was filtered and discarded. The organics were then washed with water and brine, dried (MgSO4), filtered and concentrated to afford a brown oil. This was purified by silica chromatography (eluting with 0-100% ethyl acetate in petrol) to yield 3,4-bis(benzyloxy)-6-{[6-(trifluoromethyl)pyridin-3-yl]ethynyl}pyridazine as a yellow amorphous solid (yield=10%)

Workup

  1. customThe reaction mixture was then purged
  2. customevacuated with nitrogen
  3. customfor 1 hour
  4. temperatureUpon cooling the reaction mixture
  5. customwas partitioned between ethyl acetate and water, at which point a solid
  6. customformed which
  7. filtrationwas filtered
  8. washThe organics were then washed with water and brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford a brown oil
  13. customThis was purified by silica chromatography (eluting with 0-100% ethyl acetate in petrol)

Sources & evidence

ORD record
ord-908c5a56eb844d7baec0f17df6afa508
Source dataset
uspto-grants-2016_03
Patent number
US09290456B2

Reaction notes

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