Triethylamine → cyclopropylmethyl-4-((1R,2S)-2-{2-[4-(2-azetidin-1-yl-2-oxoethyl)-3-fluorophenoxy]ethyl}cyclopropyl)piperidine-1-carboxylate

To a stirred solution of 4-((1R,2S)-2-{2-[4-(2-azetidin-1-yl-2-oxoethyl)-3-fluorophenoxy]ethyl)cyclopropyl)piperidine (Step B, Example 11; 0.30 g, 0.93 mmol) in dichloromethane (4.6 mL) under a nitrogen atmosphere was added triethylamine (0.36 mL, 2.6 mmol) and cyclopropylmethyl 2,5-dioxopyrrolidin-1-yl carbonate (0.35 g, 1.67 mmol). The resulting solution was stirred for 18 h at ambient temperature. The solution was diluted with saturated NH4Cl(aq.) (10 mL). The resulting layers were separated and the aqueous phase extracted with dichloromethane (2×30 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the obtained residue by CombiFlash chromatography (12 g silica gel, 0 to 25% EtOAc in heptane) provided the title compound as an off white semi-solid. LC/MS (m/z): 459.3 (M+H)+. GPR119 Human EC50: 2.0 nM.

1. customThe resulting layers were separated
2. extractionthe aqueous phase extracted with dichloromethane (2×30 mL)
3. dry with materialThe combined organic extracts were dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customPurification of the obtained residue by CombiFlash chromatography (12 g silica gel, 0 to 25% EtOAc in heptane)

ORD-Eintrag

ord-345ade8f6a6b415c9f5ab7fef37ad50a

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08957062B2