Tetravinylstannane → 3-Isopropyl-6-vinyl-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1929960Notes

Reaction equation

HRID 1929960 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([CH3:13])[CH3:12])=[N:9][N:10]=2)[N:7]=1.[CH:14]([Sn](C=C)(C=C)C=C)=[CH2:15].[Cl-].[Li+]>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.CN(C=O)C>[CH:11]([C:8]1[N:6]2[N:7]=[C:2]([CH:14]=[CH2:15])[CH:3]=[CH:4][C:5]2=[N:10][N:9]=1)([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 66189TetravinylstannaneHCID 433294Lithium ChlorideHCID 397324056-Chloro-3-(propan-2-yl)-[1,2,4]triazolo[4,3-b]pyridazine

Product 1

HCID 579298913-Isopropyl-6-vinyl-[1,2,4]triazolo[4,3-b]pyridazineYield 39.9%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

The 6-chloro-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (8.60 g, 43.7 mmol, Preparation #G.1), tetravinylstannane (11.91 g, 52.50 mmol), PdCl2(PPh3)2 (3.07 g, 4.37 mmol) and lithium chloride (3.71 g, 87.0 mmol) were added to DMF (65 mL) and then the mixture was heated to about 85° C. for about 1 h. The reaction was cooled to ambient temperature and then concentrated under reduced pressure. Water and EtOAc were added to the residue and then the mixture was filtered through Celite®. The filtrate was transferred to a separatory funnel and the layers were separated then the aqueous layer was extracted with EtOAc. The combined organic solutions were dried over MgSO4 and filtered prior to concentrating under reduced pressure to provide an oil which was purified by flash chromatography on silica gel with EtOAc as an eluent. The material was purified further by flash chromatography on silica gel with DCM/MeOH (95:5) as an eluent to give the title compound (3.28 g, 39.8%) as a light yellow oil which crystallized on standing: 1H NMR (DMSO-d6) δ 1.39 (d, 6H), 3.53 (m, 1H), 5.84 (d, 1H), 6.44 (d, 1H), 6.82 (dd, 1H), 7.69 (d, 1H), 8.28 (d, 1H); LC/MS (Table 1, Method a) Rt=2.06 min; MS m/z: 189.2 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. concentrationconcentrated under reduced pressure
  3. additionWater and EtOAc were added to the residue
  4. filtrationthe mixture was filtered through Celite®
  5. customThe filtrate was transferred to a separatory funnel
  6. customthe layers were separated
  7. extractionthe aqueous layer was extracted with EtOAc
  8. dry with materialThe combined organic solutions were dried over MgSO4
  9. filtrationfiltered
  10. concentrationto concentrating under reduced pressure
  11. customto provide an oil which
  12. customwas purified by flash chromatography on silica gel with EtOAc as an eluent
  13. customThe material was purified further by flash chromatography on silica gel with DCM/MeOH (95:5) as an eluent

Sources & evidence

ORD record
ord-d9ef541852284448a991108680398483
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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