Hydrochloric Acid → HCID 67314578, compound

A solution of 5-fluoro-1,3-dihydro-indol-2-one (75 mg, 0.49 mmol) in THF (4 mL) is treated with a solution of lithium bis(trimethylsilyl)amide (0.8 mL of a 1M solution in THF, 0.8 mmol) dropwise. The resulting solution is stirred at room temperature for 10 min. A solution of 2-(4-hydroxy-piperidin-2-ylmethyl)-7H-furo[3,4-b]pyridin-5-one (70 mg, 0.28 mmol) in THF (2 mL) is added dropwise to the reaction mixture. The resulting solution is stirred for 6 h. The reaction mixture is treated with additional lithium bis(trimethylsilyl)amide (0.3 mL of a 1M solution in THF, 0.3 mmol) dropwise and the reaction mixture is stirred at room temperature overnight. The reaction mixture is poured into a cold aqueous 10% HCl solution (7 mL). The resulting mixture is heated to 50° C. for 1 h and then poured into 100 mL ice water. Solid NaHCO3 is carefully added to adjust the pH to 8. The aqueous layer is extracted with EtOAc (2×). The combined organic extracts are dried with Na2SO4, filtered and concentrated. The residue is purified by chromatography (silica gel, MeOH-Chloroform). The product containing fractions are concentrated to give the title compound as a yellow solid (11 mg, 10%).

1. stirringThe resulting solution is stirred for 6 h
2. stirringis stirred at room temperature overnight
3. temperatureThe resulting mixture is heated to 50° C. for 1 h
4. extractionThe aqueous layer is extracted with EtOAc (2×)
5. dry with materialThe combined organic extracts are dried with Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue is purified by chromatography (silica gel, MeOH-Chloroform)
9. additionThe product containing fractions
10. concentrationare concentrated

ORD record

ord-0002b5ac3991404ab05957e154a92a27

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08455535B2