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Diethyl (((4-(3-oxomorpholino)phenyl)azanediyl)bis(3-(1,3- dioxoisoindolin-2-yl)propane-1,2-diyl)) bis(carbonate) and process for preparing thereof

IP.com Disclosure Number: IPCOM000234934D
Publication Date: 2014-Feb-17
Document File: 2 page(s) / 71K

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The IP.com Prior Art Database

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  Diethyl (((4-(3-oxomorpholino)phenyl)azanediyl)bis(3-(1,3- dioxoisoindolin-2-yl)propane-1,2-diyl)) bis(carbonate) and process for preparing thereof

Disclosed herein after is an impurity in the synthesis of ( (S)-2-((2-oxo-3-(4-(3- oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione (Compound I) having the following structure:

2,2'-(((4-(3-oxomorpholino)phenyl)azanediyl)bis(2-hydroxypropane-3,1- diyl))bis(isoindoline-1,3-dione) (Compound A) which was identified as a process intermediate (IPCOM000233194D) can react further to form diethyl (((4-(3- oxomorpholino)phenyl)azanediyl)bis(3-(1,3-dioxoisoindolin-2-yl)propane-1,2-diyl)) bis(carbonate) (Compound B).

Compound B can be obtained by a process as shown in the scheme below:

Example:

A reactor of 1L was loaded with Compound A (10 g, 0.017 mol), N, N'- carbonyldiimidazole (97% assay, 5.6 g, 0.034 mol) and toluene (300 ml). The suspension was heated and stirred at 114 °C (Tj) for ~5h. The reaction mixture was then cooled to 60 °C (Tj) and abs. EtOH (100 ml) was added followed by cooling to 25 °C (Tj). The mixture was concentrated under reduced pressure and the residue was


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purified by column chromatography eluted with EtOAc:hexane (gradient: 1:1→13:10→15:10→2:1→25:10→3:1 v/v→100% EtOAc) to give pure Compound B

The NMR data assignment was aided by several two-dimensional spectra including COSY, HMQC and HMBC analyses.

1H NMR (700 MHz, d6-DMSO) ppm δ 1.02 (t, 6H, J = 7 Hz), 3....