Iodine → 2-Amino-5-iodobenzonitrile

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Reaction Steps

Accordingly, the basic raw material selected for the synthesis of Lapatinib of formula-(1) is commercially available 2-amino benzonitrile of formula-(6), which reacts with iodine or iodinemonochloride to get 2-amino-5-iodobenzonitrile of the formula-(7). The compound of the formula-(7) on reaction with a novel compound N1-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-N,N-dimethylformamidine (8) at elevated temperature gives the compound N-[3-chloro-4-[(3-fluorobenzyloxy)phenyl]-6-iodo-quinazolinamine of formula-(3), The compound of the formula-(3) on reaction with 5-formyl-2-furyl boronic acid, in presence of triethylamine and Pd/C gives the compound 5-[4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-quinazolinyl)-furan-2-carbaldehyde of the formula-(4). The compound of the formula-(4), on reaction with 2-methanesulfonylethylamine hydrochloride gives the novel compound N[3-chloro-4[(3-fluorobenzyloxy]phenyl[-6-[5-({[2-methanesulphonyl)-ethyl]imino}-2-furyl]-4-quinazolinamine of the formula-(9). The novel imine compound of formula-(9) on reduction, using sodium borohydride gives the compound of the formula-(1), which is Lapatinib base. The reaction scheme of the present invention is as given the following Scheme-(C).

Provenance & Evidence