4-Fluorobenzyl chloride → 3-Cyano-1-(4-fluoro-benzyl)-6-hydroxy-7-oxo-1,7-dihydro-pyrazolo[1,5-a]pyrimidine-5-carboxylic acid 4-fluoro-benzylamide

温度

90 °C

Sodium hydride (11.0 mg, 0.367 mmol) was added in one portion to a stirred suspension of 3-Cyano-6-hydroxy-7-oxo-1,7-dihydro-pyrazolo[1,5-a]pyrimidine-5-carboxylic acid 4-fluoro-benzylamide compound with 4-fluorobenzylamine (Example 3.1) (100 mg, 0.306 mmol) in DMF (2 mL) under nitrogen at room temperature. The mixture was stirred for 30 min before p-fluorobenzyl chloride (40 μL, 0.366 mmol) was added and the mixture heated at 90° C. for 2 days. After this time, the reaction was cooled to room temperature and partitioned between ethyl acetate (10 mL) and aqueous hydrochloric acid (1M, 10 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organics were washed with water (3×10 mL), brine (10 mL) and then concentrated. The residue was purified by column chromatography (95:5:1 dichloromethane:methanol: aqueous ammonia) to afford the desired product (50 mg, 36%).

1. additionwas added
2. temperatureAfter this time, the reaction was cooled to room temperature
3. custompartitioned between ethyl acetate (10 mL) and aqueous hydrochloric acid (1M, 10 mL)
4. customThe organic layer was separated
5. extractionthe aqueous layer was extracted with ethyl acetate (3×10 mL)
6. washThe combined organics were washed with water (3×10 mL), brine (10 mL)
7. concentrationconcentrated
8. customThe residue was purified by column chromatography (95:5:1 dichloromethane:methanol: aqueous ammonia)

ORDレコード

ord-3003eca09637431080807f027926dd36

出典データセット

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08859563B2