Dichloromethane → 6-(5-chloro-2-fluoropyridin-4-yl)-N2-((tetrahydro-2H-pyran-4-yl)methyl)pyrazine-2,3-diamine

HRID 1963939

Reaktionsgleichung

Br[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[C:5]([NH2:16])=[N:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[Cl:23][C:24]1[C:25](B(O)O)=[CH:26][C:27]([F:30])=[N:28][CH:29]=1.C(Cl)Cl>COCCOC.CCOC(C)=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]>[Cl:23][C:24]1[C:25]([C:2]2[N:7]=[C:6]([NH:8][CH2:9][CH:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[C:5]([NH2:16])=[N:4][CH:3]=2)=[CH:26][C:27]([F:30])=[N:28][CH:29]=1

Komponenten

Reaktionsbedingungen

Temperatur: 100 °C

Versuchsvorschrift

To a degassed suspension of 6-bromo-N2-((tetrahydro-2H-pyran-4-yl)methyl)pyrazine-2,3-diamine (100 mg, 0.348 mmol), Na2CO3 (96 mg, 0.905 mmol) and 5-chloro-2-fluoropyridin-4-ylboronic acid (92 mg, 0.522 mmol) in DME (3 ml) was added PdCl2(dppf).CH2Cl2 adduct (22.75 mg, 0.028 mmol). The reaction mixture was capped in a flask and heated to 100° C. for 4 hr an oil bath. The reaction mixture was diluted with EtOAc and washed with H2O, sat NaCl. The organic layer was dried Na2SO4, filtered and concentrated. The crude was purified by column chromatography on silica gel (100% EtOAc/Hexane) to yield 6-(5-chloro-2-fluoropyridin-4-yl)-N2-((tetrahydro-2H-pyran-4-yl)methyl)pyrazine-2,3-diamine (34 mg, 0.101 mmol, 28.9% yield).). LCMS (m/z): 338.2 (MH+), retention time=0.65 min.

Aufarbeitung

customThe reaction mixture was capped in a flask
washwashed with H2O
filtrationfiltered
concentrationconcentrated
customThe crude was purified by column chromatography on silica gel (100% EtOAc/Hexane)

Quellen und Nachweise

ORD-Eintrag: ord-3bec5ea4a4b94fb8972a37219ccb866a
Quelldatensatz: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08415381B2

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