Reacción #68616

Ecuación de reacción

6-((5-chloroisoxazolo[4,5-b]pyridin-3-yl)difluoromethyl)quinoline

dimethylacetamide

5-bromo-3-methylisothiazole

isopropylmagnesium lithium chloride

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product

Rendimiento 3.5%

6-(difluoro(5-(3-methylisothiazol-5-yl)isoxazolo[4,5-b]pyridin-3-yl)methyl)quinoline

Rendimiento 3.5%

Disolventes

ethyl acetate

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas brought to room temperature
2. 2
   workup.STIRRINGstirred for thirty minutes
3. 3
   workup.STIRRINGThe mixture was stirred at 50° C. for ninety minutes
4. 4
   Lavadowashed with water
5. 5
   SecadoOrganic extracts were dried over magnesium sulfate
6. 6
   Otropurified by MPLC (
7. 7
   Lavadoeluted with a gradient of 10 to 50% ethyl acetate in hexanes),
8. 8
   Otrothen purified by HPLC (
9. 9
   Lavadoeluted with a gradient of 15 to 90% acetonitrile in water)

Procedimiento

To a solution of 5-bromo-3-methylisothiazole (0.19 g, 1.1 mmol) in anhydrous THF (3 mL) was added isopropylmagnesium lithium chloride (1.0 M in THF, 1.5 mL, 1.5 mmol) at −40° C. The mixture was stirred at −40° C. for twenty minutes followed by the addition of zinc chloride (0.5 M in THF, 3.1 mL, 1.6 mmol). The mixture was brought to room temperature and stirred for thirty minutes followed by the addition of Q-Phos (0.12 g, 0.17 mmol), Pd2(dba)3 (0.097 g, 0.110 mmol), 6-((5-chloroisoxazolo[4,5-b]pyridin-3-yl)difluoromethyl)quinoline (0.10 g, 0.30 mmol), and anhydrous dimethylacetamide (3.5 mL). The mixture was stirred at 50° C. for ninety minutes then was diluted with ethyl acetate and washed with water. Organic extracts were dried over magnesium sulfate and purified by MPLC (eluted with a gradient of 10 to 50% ethyl acetate in hexanes), then purified by HPLC (eluted with a gradient of 15 to 90% acetonitrile in water) to afford the product as a white solid (4.2 mg, 3%). MS m/z=395.2 [M+1]+ Calc'd for C23H15F2N3O: 394.4.

Fuente