Sodium Carbonate → 5,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine

HRID 911142Notes

Reaction equation

HRID 911142 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:11]1[C:20]2[C:15](=[C:16]([F:22])[CH:17]=[CH:18][C:19]=2[F:21])[C:14]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]3[C:36]([C:37]4[CH:42]=[CH:41][N:40]=[C:39]([NH:43][CH3:44])[N:38]=4)=[CH:35][CH:34]=[CH:33][N:32]=3)=[CH:26][CH:25]=2)=[N:13][N:12]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>CCOC(C)=O.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]>[F:21][C:19]1[CH:18]=[CH:17][C:16]([F:22])=[C:15]2[C:20]=1[C:11]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[N:12][N:13]=[C:14]2[NH:23][C:24]1[CH:25]=[CH:26][C:27]([O:30][C:31]2[C:36]([C:37]3[CH:42]=[CH:41][N:40]=[C:39]([NH:43][CH3:44])[N:38]=3)=[CH:35][CH:34]=[CH:33][N:32]=2)=[CH:28][CH:29]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 66827Phenylboronic AcidHCID 57756224HCID 57756224, compound

Product 1

HCID 577562545,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To phenylboronic acid (0.030 g, 0.24 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (0.0060 g, 0.0081 mmol) and 4-chloro-5,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)phthalazin-1-amine (0.080 g, 0.16 mmol) was added dioxane (0.35 mL) and sodium carbonate (2.0 M, aqueous) (0.16 ml, 0.33 mmol). The resulting mixture was heated to 85° C. in a sealed tube for 60 minutes. The reaction was diluted with EtOAc and water, and the layers were separated and the organic layers were dried over sodium sulfate, filtered and concentrated. The crude was purified by ISCO silica gel chromatography (20-100% EtOAc/hexanes; 40 g column). Concentrated product fractions to yield 5,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine as an off-white solid. MS m/z=534 [M+H]+. Calc'd for C30H21F2N7O: 533.54.

Workup

  1. customthe layers were separated
  2. dry with materialthe organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified by ISCO silica gel chromatography (20-100% EtOAc/hexanes; 40 g column)

Sources & evidence

ORD record
ord-648b183325c84f808319276ffbbdf521
Source dataset
uspto-grants-2011_09
Patent number
US08022221B2

Reaction notes

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