Diethyl Ether → (2-Amino-5-bromopyridin-3-yl)(6-fluoropyridin-2-yl)methanone

To a solution of 2-bromo-6-fluoropyridine (7.5 g, 42.6 mmol) in tetrahydrofuran (50 ml) at 0° C. was added a 2 M solution of isopropylmagnesium chloride in ether (21.3 ml, 42.6 mmol) over a period of 10 minutes. The ice-bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The resulting solution was added dropwise to a solution of 2-amino-5-bromo-N-methoxy-N-methylnicotinamide (3 g, 11.5 mmol) in tetrahydrofuran (40 ml) at room temperature over a period of 30 minutes. The resulting solution was stirred at room temperature for 18 hours. The solution was quenched by addition of an aqueous saturated solution of ammonium chloride at 0° C. and the mixture was stirred at room temperature for 20 minutes. Water was added and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (ISCO Companion□, 80 g column, 0-100% EtOAc/Petrol) to give an orange sticky solid which was slurried in ether/MeOH, collected by filtration and dried. The desired compound was obtained as a yellow solid (196 mg, 6% yield).

1. customThe ice-bath was removed
2. stirringThe resulting solution was stirred at room temperature for 18 hours
3. customThe solution was quenched by addition of an aqueous saturated solution of ammonium chloride at 0° C.
4. stirringthe mixture was stirred at room temperature for 20 minutes
5. additionWater was added
6. extractionthe mixture was extracted with ethyl acetate
7. dry with materialThe organic layer was dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified on silica gel by flash column chromatography (ISCO Companion□, 80 g column, 0-100% EtOAc/Petrol)
11. customto give an orange sticky solid which
12. filtrationcollected by filtration
13. customdried

ORD record

ord-93a7998b14f74cf08417ecb42de90cd7

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08741931B2