Potassium Phosphate, Tribasic → HCID 86684005, compound

HRID 1185148Notes

Reaction equation

HRID 1185148 reaction equation
[F:1][CH:2]([F:31])[CH2:3][N:4]1[CH2:9][CH2:8][N:7]2[N:10]=[C:11]([NH:13][C:14]3[C:15](=[O:30])[N:16]([CH3:29])[CH:17]=[C:18](B4OC(C)(C)C(C)(C)O4)[CH:19]=3)[CH:12]=[C:6]2[CH2:5]1.[C:32]([C:36]1[CH:37]=[C:38]2[C:43](=[C:44]([F:46])[CH:45]=1)[C:42](=[O:47])[N:41]([C:48]1[N:55]=[CH:54][CH:53]=[C:52](Cl)[C:49]=1[CH:50]=[O:51])[N:40]=[CH:39]2)([CH3:35])([CH3:34])[CH3:33].[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:32]([C:36]1[CH:37]=[C:38]2[C:43](=[C:44]([F:46])[CH:45]=1)[C:42](=[O:47])[N:41]([C:48]1[N:55]=[CH:54][CH:53]=[C:52]([C:18]3[CH:19]=[C:14]([NH:13][C:11]4[CH:12]=[C:6]5[CH2:5][N:4]([CH2:3][CH:2]([F:31])[F:1])[CH2:9][CH2:8][N:7]5[N:10]=4)[C:15](=[O:30])[N:16]([CH3:29])[CH:17]=3)[C:49]=1[CH:50]=[O:51])[N:40]=[CH:39]2)([CH3:35])([CH3:33])[CH3:34]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehydeHCID 86684006HCID 86684006, compound

Product 1

HCID 86684005HCID 86684005, compoundYield 38%

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 25-mL round-bottomed flask equipped with a reflux condenser was charged with 135d (200 mg, 0.46 mmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (166 mg, 0.46 mmol), K3PO4 (195 mg, 0.92 mmol), sodium acetate (75 mg, 0.92 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (17 mg, 0.023 mmol), and acetonitrile/water (8/0.2 mL). After three cycles of vacuum/N2 flush, the mixture was 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 diluted with dichloromethane (30 mL) and water (15 mL). The water layer was extracted with dichloromethane (2×15 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 135e (110 mg, 38%) as a yellow solid. MS-ESI: [M+H]+ 633.3

Workup

  1. customA 25-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/N2 flush
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiondiluted with dichloromethane (30 mL) and water (15 mL)
  5. extractionThe water layer was extracted with dichloromethane (2×15 mL)
  6. extractionThe combined organic extract
  7. dry with materialwas dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe dark residue was purified by silica-gel column chromatography
  11. washeluting with dichloromethane/methanol (80/1 to 30/1)

Sources & evidence

ORD record
ord-d35a493b478242eb96069c099e62966c
Source dataset
uspto-grants-2014_03
Patent number
US08669251B2

Reaction notes

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