Potassium Phosphate, Tribasic → HCID 86683999, compound

HRID 407729Notes

Reaction equation

HRID 407729 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[CH:31]=[C:21]3[CH2:22][N:23]([CH2:26][C:27]([F:30])([F:29])[F:28])[CH2:24][CH2:25][N:20]3[N:19]=2)[C:3]1=[O:32].[C:33]([C:37]1[CH:38]=[C:39]2[C:44](=[C:45]([F:47])[CH:46]=1)[C:43](=[O:48])[N:42]([C:49]1[N:56]=[CH:55][CH:54]=[C:53](Cl)[C:50]=1[CH:51]=[O:52])[N:41]=[CH:40]2)([CH3:36])([CH3:35])[CH3:34].[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:33]([C:37]1[CH:38]=[C:39]2[C:44](=[C:45]([F:47])[CH:46]=1)[C:43](=[O:48])[N:42]([C:49]1[N:56]=[CH:55][CH:54]=[C:53]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[CH:31]=[C:21]5[CH2:22][N:23]([CH2:26][C:27]([F:29])([F:28])[F:30])[CH2:24][CH2:25][N:20]5[N:19]=4)[C:3](=[O:32])[N:2]([CH3:1])[CH:7]=3)[C:50]=1[CH:51]=[O:52])[N:41]=[CH:40]2)([CH3:36])([CH3:34])[CH3:35]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehydeHCID 86684000HCID 86684000, compound

Product 1

HCID 86683999HCID 86683999, compoundYield 45%

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 134d (200 mg, 0.44 mmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (159 mg, 0.44 mmol), K3PO4 (186 mg, 0.88 mmol), sodium acetate (72 mg, 0.88 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (16 mg, 0.022 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 under N2 protection. 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 separated and 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 134e (128 mg, 45%) as a yellow solid. MS-ESI: [M+H]+ 651.3

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. customThe water layer was separated
  6. extractionextracted with dichloromethane (2×15 mL)
  7. extractionThe combined organic extract
  8. dry with materialwas 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 30/1)

Sources & evidence

ORD record
ord-ac326b914ba74ff28987ad02de923ea0
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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