Hydrochloric Acid → N-(4-(3-Benzylpyrazin-2-yloxy)phenyl)pyridin-2-amine
Reaktionsgleichung
Cl[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[Br-].[CH2:23]([Zn+])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1COCC1.Cl>>[CH2:23]([C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1Komponenten
Reaktionsbedingungen
- Temperatur
- 70 °C
Versuchsvorschrift
A suspension of N-(4-(3-chloropyrazin-2-yloxy)phenyl)pyridin-2-amine (200 mg, 0.670 mmol), benzylzinc bromide, 0.5M in THF (6.7 mL, 3.35 mmol), and bis(di-t-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (80 mg, 0.11 mmol) was sparged with argon for 5 minutes then heated to 70° C. for 2 h. The reaction was then partitioned between EtOAc (30 mL) and sat NH4Cl (10 mL). The separated organic layer was dried over MgSO4, concentrated under reduced pressure, then purified on silica (40 g) eluting with 1.5-2.0% MeOH/DCM. The resulting residue was then dissolved in MeOH (5 mL) and 0.105 mL of HCl (5 M; 0.105 mL, 0.525 mmol) added. The resulting solid was isolated by filtration to give the title compound. MS (ESI positive ion) m/z: 355.1 (M+1). IC50 (uM) 0.250.
Aufarbeitung
- customThe reaction was then partitioned between EtOAc (30 mL)
- dry with materialThe separated organic layer was dried over MgSO4
- concentrationconcentrated under reduced pressure
- custompurified on silica (40 g)
- washeluting with 1.5-2.0% MeOH/DCM
- dissolutionThe resulting residue was then dissolved in MeOH (5 mL)
- customThe resulting solid was isolated by filtration
Quellen und Nachweise
- ORD-Eintrag
- ord-adeed2dc030f40139f78929909584496
- Quelldatensatz
- uspto-grants-2014_01
- Patentnummer
- US08637500B2
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