Iodine → 2-Amino-5-iodobenzonitrile
Reaction equation
CS(CCNCC1OC([C:14]2[CH:15]=[CH:16][C:17]3[N:23]=C[N:21]=[C:20](NC4C=CC(OCC5C=CC=C(F)C=5)=C(Cl)C=4)[C:18]=3[CH:19]=2)=CC=1)(=O)=O.NC1C=CC=CC=1C#N.[I:50]I.ICl>>[NH2:23][C:17]1[CH:16]=[CH:15][C:14]([I:50])=[CH:19][C:18]=1[C:20]#[N:21]Participants
Procedure
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).
Sources & evidence
- ORD record
- ord-460908082bbd4e0fb0c473b9d5b8f36c
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08664389B2
Reaction notes
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