- Preparation method of lenalidomide
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A preparation method of lenalidomide comprises the following steps: 1, reacting a raw material methyl 2-methyl-3-nitro-benzoate with a halogenating reagent to obtain methyl 2-halomethyl-3-nitro-benzoate represented by formula (I); 2, reacting the methyl 2-halomethyl-3-nitro-benzoate with dimethyl D,L-glutamate hydrochloride in the presence of an alkaline compound to obtain dimethyl 3-(7-nitro-1-oxo-1,3-dihydroisoindole-2-yl)glutarate represented by formula (II); 3, hydrolyzing the above compound of formula (II) to obtain 3-(7-nitro-1-oxo-1,3-dihydroisoindole-2-yl)glutaric acid represented by formula (III); 4, reducing the above compound of formula (III) to obtain 3-(7-amino-1-oxo-1,3-dihydroisoindole-2-yl)glutaric acid represented by formula (IV); and 5, carrying out ring closure on the above compound of formula (IV) to obtain lenalidomide represented by formula (V). The method has the advantages of simple process, high safety, cheap and easily available raw materials, good quality of the above product, and suitableness for industrial production.
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- METHODS FOR SYNTHESIZING 3-(SUBSTITUTED DIHYDROISOINDOLINONE-2-YL)-2,6-DIOXOPIPERIDINE, AND INTERMEDIATES THEREOF
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The present invention discloses methods for synthesizing 3-(substituted dihydroisoindolinone-2-yl)-2,6-dioxopiperidine and intermediates thereof, namely, the synthesis of compounds of the Formula (I), with each substitutional group defined in the patent specification. Owing to the advantages of high productivity, little influence to the environment and material accessibility, the methods of the present invention is suitable for industrial production.
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Page/Page column 41
(2010/12/29)
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- METHOD FOR THE PRODUCTION OF SUBSTITUTED 2,6-DIOXOPIPERIDINE-3-YL COMPOUNDS
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Disclosed is a method for producing compounds of general formula (I), wherein one of the substituents R1, R2, R3, and R4 represents nitro, amino, -NHR5, or -N(R5)R6 while the remaining three substituents among R1, R2, R3, and R4 independently represent hydrogen, (C1-4) alkyl or (C1-4) alkoxy, and R5 as well as R6 independently represent (C1-4) alkyl or a protective group. According to the inventive method, a compound of general formula (II), wherein one of the substituents R'1, R'2, R'3, R'4 represents nitro, -NHR5, or -N(R5)R6 while the remaining substituents have the meaning indicated above and R7 respectively represents amino, -O-(NH4+), -OH, -O-alkyl, or linear or branched (C1-12) alkyl, is reacted so as to separate NH3 and/or water or alkyl-OH (if R7 = -O-alkyl), and optionally provided protective groups are separated.
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Page/Page column 6
(2008/06/13)
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