Phosphorus oxychloride → 5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

17.3 g (60.0 mmol) of the compound obtained in Example 7 were heated to 103°-107° C. in 40.5 ml of sulpholane and 5.4 ml of acetonitrile. Thereafter, 6.9 g (45.0 mmol) of phosphorus oxychloride were slowly added dropwise while stirring, the dropping funnel was rinsed with 2.8 ml of acetonitrile, then the mixture was stirred at 107° C. for 1.5 h until conversion was complete (HPLC). Thereafter, the mixture was cooled to room temperature, and 2.8 ml of sulpholane/acetonitrile (5:1 vol/vol) and then 17.8 ml of water were added dropwise. The mixture was stirred for 0.5 h, a solution of 9.4 g of aqueous ammonia (28%) in 22.7 ml of water was added dropwise and the mixture was stirred for a further 2 h. The precipitated solids were filtered off with suction, washed three times with 20.5 ml each time of water and dried in a vacuum drying cabinet at 50° C. under a gentle nitrogen stream. This gave 14.7 g (91.9% of theory) of the title compound.

1. washthe dropping funnel was rinsed with 2.8 ml of acetonitrile
2. stirringthe mixture was stirred at 107° C. for 1.5 h until conversion
3. addition2.8 ml of sulpholane/acetonitrile (5:1 vol/vol) and then 17.8 ml of water were added dropwise
4. stirringThe mixture was stirred for 0.5 h
5. additiona solution of 9.4 g of aqueous ammonia (28%) in 22.7 ml of water was added dropwise
6. stirringthe mixture was stirred for a further 2 h
7. filtrationThe precipitated solids were filtered off with suction
8. washwashed three times with 20.5 ml each time of water
9. customdried in a vacuum
10. customdrying cabinet at 50° C. under a gentle nitrogen

ORD record

ord-5a3cf2fd7b634d2a9db409d2782459e1

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802847B2