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

HRID 593957Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 593957
[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

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 66827Phenylboronic AcidHCID 577562244-chloro-5,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)phthalazin-1-amine

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-b9dcafdc31b942c8b34d36f3fa512888
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242961B2

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