Potassium Phosphate, Tribasic → HCID 86683954, compound

HRID 407670Notes

Reaction equation

HRID 407670 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[S:19][C:20]([CH3:23])=[CH:21][N:22]=2)[C:3]1=[O:24].[C:25]([C:29]1[CH:30]=[C:31]2[C:36](=[C:37]([F:39])[CH:38]=1)[C:35](=[O:40])[N:34]([C:41]1[N:48]=[CH:47][CH:46]=[C:45](Cl)[C:42]=1[CH:43]=[O:44])[N:33]=[CH:32]2)([CH3:28])([CH3:27])[CH3:26].[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].O.C(#N)C>[C:25]([C:29]1[CH:30]=[C:31]2[C:36](=[C:37]([F:39])[CH:38]=1)[C:35](=[O:40])[N:34]([C:41]1[N:48]=[CH:47][CH:46]=[C:45]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[S:19][C:20]([CH3:23])=[CH:21][N:22]=4)[C:3](=[O:24])[N:2]([CH3:1])[CH:7]=3)[C:42]=1[CH:43]=[O:44])[N:33]=[CH:32]2)([CH3:28])([CH3:26])[CH3:27]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehydeHCID 86683955HCID 86683955, compound

Product 1

HCID 86683954HCID 86683954, compoundYield 55.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 120b (174 mg, 0.50 mmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (180 mg, 0.50 mmol), K3PO4 (212 mg, 1.0 mmol), sodium acetate (82 mg, 1.0 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (18 mg, 0.025 mmol), acetonitrile (8 mL), and water (0.5 mL). The reaction mixture was subjected to three cycles of vacuum/argon flush and heated at 100° C. for 1 h. Analysis of the reaction mixture by LCMS showed complete conversion to the desired product. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was diluted with dichloromethane (50 mL) and water (30 mL). The water layer was extracted with dichloromethane (2×30 mL). The combined organic extract 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 30:1) to afford 120c (150 mg, 55%) as a yellow solid. MS-ESI: [M+H]+ 545.3

Workup

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customflush
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. additionThe residue was diluted with dichloromethane (50 mL) and water (30 mL)
  7. extractionThe water layer was extracted with dichloromethane (2×30 mL)
  8. extractionThe combined organic extract
  9. dry with materialwas dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe dark residue was purified by silica-gel column chromatography
  13. washeluting with dichloromethane/methanol (80:1 to 30:1)

Sources & evidence

ORD record
ord-d2993485d8814e17b1744f9458132df1
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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