Sodium Carbonate → 4-phenyl-N-(4-(5-(pyridin-4-yl)pyrimidin-4-yloxy)phenyl)phthalazin-1-amine

HRID 227801Notes

Reaction equation

HRID 227801 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.I[C:11]1[C:12]([O:17][C:18]2[CH:23]=[CH:22][C:21]([NH:24][C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[C:28]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[N:27][N:26]=3)=[CH:20][CH:19]=2)=[N:13][CH:14]=[N:15][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(Cl)Cl.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:35]1([C:28]2[C:29]3[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:25]([NH:24][C:21]3[CH:22]=[CH:23][C:18]([O:17][C:12]4[C:11]([C:4]5[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=5)=[CH:16][N:15]=[CH:14][N:13]=4)=[CH:19][CH:20]=3)=[N:26][N:27]=2)[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 66731498N-(4-(5-iodopyrimidin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine

Product 1

HCID 577562424-phenyl-N-(4-(5-(pyridin-4-yl)pyrimidin-4-yloxy)phenyl)phthalazin-1-amine

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A slurry of 4-pyridylboronic acid (0.0950 g, 0.773 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (0.0141 g, 0.0193 mmol), and N-(4-(5-iodopyrimidin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine (0.200 g, 0.387 mmol) and sodium carbonate 2.0 M in H2O (0.387 ml, 0.773 mmol) in 1.5 mL dioxane was flushed with nitrogen, sealed, and heated to 80° C. The reaction became dark and solids dissolved after 1 h. After 3 h, the reaction was judged complete. The reaction was cooled and diluted with DCM and water. The resulting aqueous emulsion was extracted 4× DCM. The combined organics were dried over anhyd sodium sulfate, filtered, and concentrated in vacuo. The material was adsorbed onto 1.8 g silica gel from MeOH/DCM, dried, and purified by silica gel chromatography (0-60-100% 90/10 DCM/MeOH in DCM) to give 4-phenyl-N-(4-(5-(pyridin-4-yl)pyrimidin-4-yloxy)phenyl)phthalazin-1-amine as a tan solid. MS m/z=469 [M+H]+. Calc'd for C29H20N6O: 468.5.

Workup

  1. customsealed
  2. dissolutionsolids dissolved after 1 h
  3. temperatureThe reaction was cooled
  4. extractionThe resulting aqueous emulsion was extracted 4× DCM
  5. dry with materialThe combined organics were dried over anhyd sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customdried
  9. custompurified by silica gel chromatography (0-60-100% 90/10 DCM/MeOH in DCM)

Sources & evidence

ORD record
ord-dda9ba6fc5e149968d7050e5c11541c6
Source dataset
uspto-grants-2009_07
Patent number
US07560551B2

Reaction notes

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