Hydrochloric Acid → HCID 67315650, Verbindung

A solution of 5-fluoro-1,3-dihydro-indol-2-one (72 mg, 0.47 mmol) in THF (2 mL) is treated with a solution of lithium bis(trimethylsilyl)amide (1.2 mL of a 1M solution in THF, 1.2 mmol) dropwise. The resulting solution is stirred for 10 min at room temperature. A solution 2-{4-[2-(2-hydroxy-ethoxy)-ethyl]-piperazin-1-ylmethyl}-7H-furo[3,4-b]pyridin-5-one (77 mg, 0.24 mmol) in THF (1.5 mL) and added dropwise to the reaction mixture. The resulting solution is stirred for 4 h and is then treated with HCl (4M in dioxane, 5 mL) at 0° C. The reaction mixture is stirred at room temperature for 48 h. The reaction mixture is concentrated and the residue is treated with saturated aqueous NaHCO3. The aqueous solution is extracted with EtOAc (2×). The combined organic extracts are dried (MgSO4) and concentrated. The residue is purified by chromatography (silica gel, gradient elution 20:1 chloroform:MeOH to 10:1 chloroform:MeOH). The product containing fractions are concentrated and the residue is triturated from EtOAc-hexane and collected by filtration to give the title compound as a yellow solid (22 mg, 20%).

1. stirringThe resulting solution is stirred for 4 h
2. stirringThe reaction mixture is stirred at room temperature for 48 h
3. concentrationThe reaction mixture is concentrated
4. additionthe residue is treated with saturated aqueous NaHCO3
5. extractionThe aqueous solution is extracted with EtOAc (2×)
6. dry with materialThe combined organic extracts are dried (MgSO4)
7. concentrationconcentrated
8. customThe residue is purified by chromatography (silica gel, gradient elution 20:1 chloroform:MeOH to 10:1 chloroform:MeOH)
9. additionThe product containing fractions
10. concentrationare concentrated
11. customthe residue is triturated from EtOAc-hexane
12. filtrationcollected by filtration

ORD-Eintrag

ord-af4105d778aa4c8f8a6891cc5566a8e1

Quelldatensatz

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08455535B2