Preparing bendamustine alkyl ester compounds, comprises reacting substituted 2-((2-hydroxy-ethyl)-phenyl-amino)-ethanol compounds with a mixture comprising carbonyl amine compounds and sulfonyl compounds, or diketo compounds

摘要

Preparing bendamustine alkyl ester compounds (I) or their salts, comprises reacting substituted 2-[(2-hydroxy-ethyl)-phenyl-amino]-ethanol compounds (III) with a mixture comprising carbonyl amine compounds (IV) and sulfonyl compounds (V), or diketo compounds (VI). Preparing bendamustine alkyl ester compounds of formula (I) or their salts, comprises reacting substituted 2-[(2-hydroxy-ethyl)-phenyl-amino]-ethanol compounds of formula (III) with a mixture comprising carbonyl amine compounds of formula (R6-C(=O)-N(R8)-R7) (IV) and sulfonyl compounds of formula (R9-S(=O)-R10) (V), or diketo compounds of formula (X-C(=O)-C(=O)-X) (VI). X : halo; either R1, R2 : H or CH 2(CH 2) mCOOR3, if R1 is H then R2 is CH 2(CH 2) mCOOR3, or vice versa; or R1R2 : -N=C(CH 2-(CH 2) n-COOR5)-N(R4)-; R3-R5, R7-R10 : alkyl; R6 : H or alkyl; and m, n : 0-12. An independent claim is included for preparing bendamustine compounds of formula (VII) or their salts, comprising preparing (I) by the above process, and undergoing ester hydrolysis of (I). Either R11, R12 : H or CH 2(CH 2) mCOOH, if R11 is H then R12 is CH 2(CH 2) mCOOH, or vice versa; or R11R12 : -N=C(CH 2-(CH 2) n-COOH)-N(R4)-. [Image] [Image] ACTIVITY : Cytostatic. MECHANISM OF ACTION : None given.