Reaktion #2371765

Reaktionsgleichung

6-Methyl-2-pyridylzinc bromide

5-[2-(4-fluoro-3-methylphenyl)pyridin-3-yl]-1H-indazole

2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl

→

5-(2-(6-Methylpyridin-2-yl)pyridin-3-yl)-1H-indazole

Ausbeute 47.4%

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONcontaining
2. 2
   Sonstigedegassed under vacuum
3. 3
   SonstigeAfter three degas cycles
4. 4
   Temperaturthe reaction mixture was cooled to the room temperature
5. 5
   workup.ADDITIONdiluted with Rochelle salt (5 mL)
6. 6
   Einengenconcentrated
7. 7
   Sonstigeto remove the volatiles
8. 8
   workup.ADDITIONThe concentrated aqueous solution was diluted with EtOAc (30 mL)
9. 9
   Sonstigeseparated the organic layer
10. 10
    ExtraktionAqueous solution was further extracted with EtOAc (30 mL)
11. 11
    WaschenCombined organic layers washed with aq. NaCl (10 mL)
12. 12
    workup.STIRRINGstirred over MgSO4
13. 13
    Filtrationfiltered through a pad of Florosil/celite
14. 14
    EinengenThe filtrate was concentrated
15. 15
    Sonstigepurified by preparative HPLC
16. 16
    EinengenThe collected fractions were concentrated
17. 17
    workup.ADDITIONdiluted with water and neutralized with aq. NaHCO3
18. 18
    SonstigeThe resultant solid formed
19. 19
    Filtrationwas collected by filtration
20. 20
    Sonstigedried

Vorschrift

A vial with a piercable teflon cap containing a magetic stir was charged with 5-[2-(4-fluoro-3-methylphenyl)pyridin-3-yl]-1H-indazole (0.2 g, 0.87 mmol), Pd2(dba)3(30 mg, 0.03 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPHOS, 60 mg, 0.13 mmol) under argon atmosphere. 6-Methyl-2-pyridylzinc bromide (0.5 M in THF, 4.0 mL, 2 mmol) was added to above reactants and degassed under vacuum. After three degas cycles, the reaction mixture was heated at 65° C. under argon. After 6 h, the reaction mixture was cooled to the room temperature and diluted with Rochelle salt (5 mL) and concentrated to remove the volatiles. The concentrated aqueous solution was diluted with EtOAc (30 mL) and separated the organic layer. Aqueous solution was further extracted with EtOAc (30 mL). Combined organic layers washed with aq. NaCl (10 mL), stirred over MgSO4, and filtered through a pad of Florosil/celite. The filtrate was concentrated and purified by preparative HPLC. The collected fractions were concentrated, diluted with water and neutralized with aq. NaHCO3. The resultant solid formed was collected by filtration and dried to provide 5-(2-(6-Methylpyridin-2-yl)pyridin-3-yl)-1H-indazole (118 mg, 47%) as a white solid. 1H NMR (DMSO-d6): δ 13.01 (s, 1H), 8.63 (dd, 1H, J=0.8 and 4.7 Hz), 7.99 (s, 1H), 7.89 (d, 1H, J=7.9 Hz), 7.57 (app d, 2H, J=8.5 Hz), 7.51 (dd, 1H, J=4.9 and 7.6 Hz), 7.34 (d, 1H, J=8.8 Hz), 7.26 (d, 1H, J=7.6 Hz), 7.07 (d, 1H, J=7.6 Hz), 6.97 (d, 1H, J=8.8 Hz), 2.15 (s, 3H).LCMS: rt 2.13 min (B), purity 97%, MS (m/e) 287 (MH+).

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