2-Fluoro-5-(trifluoromethyl)benzylamine → 4-Chloro-6-(2-fluoro-5-trifluoromethyl-benzylamino)-2H-phthalazin-1-one

HRID 1667449

Reaktionsgleichung

Reaktionsgleichung von HRID 1667449
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][N:6]=[C:5]2[Cl:13].[F:14][C:15]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][C:16]=1[CH2:17][NH2:18].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>CC(N(C)C)=O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:13][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([NH:18][CH2:17][C:16]3[CH:19]=[C:20]([C:23]([F:24])([F:25])[F:26])[CH:21]=[CH:22][C:15]=3[F:14])[CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Komponenten

8

Edukt 4

HCID 5338392-Fluoro-5-(trifluoromethyl)benzylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Produkt 1

HCID 584472314-Chloro-6-(2-fluoro-5-trifluoromethyl-benzylamino)-2H-phthalazin-1-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (150 mg, 0.58 mmol), 2-fluoro-5-trifluoromethyl-benzylamine (124 mg, 0.64 mmol), Pd2(dba)3 (53 mg, 0.058 mmol), rac-BINAP (132 mg, 0.17 mmol) and NaOt-Bu (140 mg, 1.45 mmol) in DMA (6 mL) was heated at 80° C. for 1 h. The mixture was allowed to cool, diluted with EtOAc (25 mL) and washed with water (25 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated. Chromatography on silica (EtOAc/hexanes) yielded the title compound. 4-Chloro-6-(2-fluoro-5-trifluoromethyl-benzylamino)-2H-phthalazin-1-one: 27 mg (12.5%): m/z (M+H)=372. 1H-NMR (DMSO-d6) δ: 12.38 (s, 1H), 7.95 (d, 1H), 7.85 (m, 1H), 7.75 (m, 1H), 7.65 (m, 1H), 7.49 (m, 1H), 7.19 (dd, 1H), 6.87 (s, 1H), 4.56 (d, 2H).

Aufarbeitung

  1. temperatureto cool
  2. washwashed with water (25 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-1c32c1489fa643bd906229098571d76d
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08044041B2

Verknüpfte Notizen

Wird geladen…