Diisopropylamine → 2-(2,4-Difluorophenyl)-6-(2-methylpyrimidin-5-yl)isonicotinic acid

HRID 1909131

Reaktionsgleichung

Cl[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[F:18])[N:10]=1)[C:5]([OH:7])=[O:6].[CH3:19][C:20]1[N:25]=[CH:24][C:23](B(O)O)=[CH:22][N:21]=1.[Na+].[Na+].[Na+].P(C1C=C(S([O-])(=O)=O)C=CC=1)(C1C=C(S([O-])(=O)=O)C=CC=1)C1C=C(S([O-])(=O)=O)C=CC=1.C(NC(C)C)(C)C>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:18][C:12]1[CH:13]=[C:14]([F:17])[CH:15]=[CH:16][C:11]=1[C:9]1[CH:8]=[C:4]([CH:3]=[C:2]([C:23]2[CH:22]=[N:21][C:20]([CH3:19])=[N:25][CH:24]=2)[N:10]=1)[C:5]([OH:7])=[O:6]

Komponenten

Reaktionsbedingungen

Temperatur: 80 °C

Versuchsvorschrift

To a solution of 2-chloro-6-(2,4-difluorophenyl)isonicotinic acid (0.10 g, 0.37 mmol) in DMF (1.9 mL) and water (0.6 mL) were added (2-methylpyrimidin-5-yl)boronic acid (0.31 g, 2.23 mmol), palladium(II)acetate (12.5 mg, 0.06 mmol), 3,3′,3″-phosphinidynetris(benzenesulfonic acid) trisodium salt (95.0 mg, 0.17 mmol) and diisopropylamine (0.19 mL, 1.30 mmol). The mixture was heated to 80° C. After 2 h, the mixture was filtered and the filtrate was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid). To the product fractions was added HCl (2.0 M in ether) and the mixture was concentrated to give the hydrochloride salt of the title compound. MS 328.1 (M+1).

Aufarbeitung

filtrationthe mixture was filtered
customthe filtrate was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid)
additionTo the product fractions was added HCl (2.0 M in ether)
concentrationthe mixture was concentrated

Quellen und Nachweise

ORD-Eintrag: ord-a6351b7a675d4686931e681a64c80b55
Quelldatensatz: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08598209B2

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