Potassium Phosphate, Tribasic → HCID 86718272, compound

HRID 407753Notes

Reaction equation

HRID 407753 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[N:24]=[CH:23][CH:22]=[C:21](Cl)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[CH3:26][N:27]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[C:29]([NH:42][C:43]2[CH:47]=[CH:46][N:45]([CH3:48])[N:44]=2)[C:28]1=[O:49].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C.O>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[N:24]=[CH:23][CH:22]=[C:21]([C:31]3[CH:30]=[C:29]([NH:42][C:43]4[CH:47]=[CH:46][N:45]([CH3:48])[N:44]=4)[C:28](=[O:49])[N:27]([CH3:26])[CH:32]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehydeHCID 86718273HCID 86718273, compound

Product 1

HCID 86718272HCID 86718272, compoundYield 53.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (359 mg, 1.0 mmol), 140b (660 mg, 2.0 mmol), K3PO4 (424 mg, 2.0 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (82 mg, 0.10 mmol), sodium acetate (164 mg, 2.0 mmol), and acetonitrile/water (15/0.2 mL). After three cycles of vacuum/N2 flush, the mixture was heated at 100° C. for 1.5 h. The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with dichloromethane (30 mL) and water (30 mL). The organic layer was separated and the aqueous extracted with dichloromethane (3×20 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80/1 to 50/1) to afford 140c (280 mg, 53%) as yellow solid. MS-ESI: [M+H]+ 528.1

Workup

  1. customA 50-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/N2 flush
  3. temperatureThe mixture was cooled to room temperature
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted with dichloromethane (30 mL) and water (30 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous extracted with dichloromethane (3×20 mL)
  8. dry with materialThe combined organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe dark residue was purified by silica-gel column chromatography
  12. washeluting with dichloromethane/methanol (80/1 to 50/1)

Sources & evidence

ORD record
ord-8380dd416ebd4248af0af5076f73ba2f
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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