Potassium Phosphate, Tribasic → HCID 86684040, compound

HRID 1185188Notes

Reaction equation

HRID 1185188 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].[C:26]([N:31]1[CH2:36][CH2:35][N:34]2[N:37]=[C:38]([NH:40][C:41]3[C:42](=[O:57])[N:43]([CH3:56])[CH:44]=[C:45](B4OC(C)(C)C(C)(C)O4)[CH:46]=3)[CH:39]=[C:33]2[CH2:32]1)(=[O:30])[CH:27]([CH3:29])[CH3:28].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>O.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>[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:45]3[CH:46]=[C:41]([NH:40][C:38]4[CH:39]=[C:33]5[CH2:32][N:31]([C:26](=[O:30])[CH:27]([CH3:28])[CH3:29])[CH2:36][CH2:35][N:34]5[N:37]=4)[C:42](=[O:57])[N:43]([CH3:56])[CH:44]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehydeHCID 86684041HCID 86684041, compound

Product 1

HCID 86684040HCID 86684040, compoundYield 37.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A 100-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 (150 mg, 0.42 mmol), 148d (278 mg, 0.63 mmol), Pd(dppf)Cl2 (17.1 mg, 0.021 mmol), K3PO4 (178.1 mg, 0.84 mmol), sodium acetate (68.9 mg, 0.84 mmol), acetonitrile (15 mL), and water (5 drops). The system was subjected to three cycles of vacuum/nitrogen flush and heated at 100° C. under N2 protection for 1 h. Analysis of the reaction mixture by LCMS showed complete conversion to the desired product. It was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was washed with acetonitrile (0.5 mL) to afford 148e as a white solid (100 mg, 37%), which was used in the next step without further purification. MS-ESI: [M+H]+ 638.8

Workup

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customflush
  3. temperatureIt was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. washThe residue was washed with acetonitrile (0.5 mL)

Sources & evidence

ORD record
ord-8e289a1257454860a922e035944ce628
Source dataset
uspto-grants-2014_03
Patent number
US08669251B2

Reaction notes

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