Sodium Carbonate → N-(4-(3-bromopyridin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine

HRID 2361067Notes

Reaction equation

HRID 2361067 reaction equation
F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[F:19][C:20]1[CH:25]=[C:24](B(O)O)[CH:23]=[CH:22][N:21]=1.[Br:29][C:30]1[CH:31]=[N:32][CH:33]=[CH:34][C:35]=1[O:36][C:37]1[CH:42]=[CH:41][C:40]([NH:43][C:44]2[C:53]3[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=3)[C:47]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[N:46][N:45]=2)=[CH:39][CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+]>CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[F:19][C:20]1[CH:25]=[C:24]([C:34]2[CH:33]=[N:32][CH:31]=[CH:30][C:35]=2[O:36][C:37]2[CH:38]=[CH:39][C:40]([NH:43][C:44]3[C:53]4[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=4)[C:47]([C:54]4[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=4)=[N:46][N:45]=3)=[CH:41][CH:42]=2)[CH:23]=[CH:22][N:21]=1.[Br:29][C:30]1[CH:31]=[N:32][CH:33]=[CH:34][C:35]=1[O:36][C:37]1[CH:42]=[CH:41][C:40]([NH:43][C:44]2[C:53]3[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=3)[C:47]([C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=3)=[N:46][N:45]=2)=[CH:39][CH:38]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 27833962-Fluoropyridine-4-boronic acidHCID 66731439N-(4-(3-bromopyridin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine

Product 2

HCID 66731439N-(4-(3-bromopyridin-4-yloxy)phenyl)-4-phenylphthalazin-1-amineHCID 66732281N-(4-(3-(2-fluoropyridin-4-yl)pyridin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A resealable reaction tube was charged with tri-tert-butylphosphonium tetrafluoroborate (0.024 g, 0.082 mmol), palladium (II) acetate (0.009 g, 0.041 mmol), 2-fluoropyridine-4-boronic acid (0.086 g, 0.614 mmol) and N-(4-(3-bromopyridin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine (0.192 mg, 0.409 mmol) and was purged with nitrogen for several minutes. 1.2 mL of dioxane and 2.0 M aqueous sodium carbonate (0.614 mL, 0.123 mmol) were added, the tube was sealed, and the reaction mixture was heated to 100° C. for 48 h. The mixture was diluted with EtOAc and washed with water. The organic portion was dried with MgSO4 and concentrated. Purification by Gilson reverse phase liquid chromatography (5-70% ACN/water/0.1% TFA over 14 min) provided N-(4-(3-(2-fluoropyridin-4-yl)pyridin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine as a mixture with the hydrodehalogenation product of N-(4-(3-bromopyridin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine.

Workup

  1. customwas purged with nitrogen for several minutes
  2. customthe tube was sealed
  3. washwashed with water
  4. dry with materialThe organic portion was dried with MgSO4
  5. concentrationconcentrated
  6. customPurification by Gilson reverse phase liquid chromatography (5-70% ACN/water/0.1% TFA over 14 min)

Sources & evidence

ORD record
ord-31fef22d972447dc96538741787736ba
Source dataset
uspto-grants-2014_04
Patent number
US08686155B2

Reaction notes

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