Synthesis of the olanzapine labeled by carbon‐14

Abstract

Olanzapine is one of the most widely used antipsychotic drugs, which acts as an antagonist for multiple neurotransmitter receptor sites. 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno [2,3-b][1,5] benzodiazepine (Olanzapine) labeled with carbon-14 in the four positions has been synthesized as part of a three-step sequence from 2-amino-5-methylthiophene-3-carbonitrile-[carbonitrile-(14) C].

Recent developments in heterocycle labeling with carbon isotopes

“…Olanzapine, commercialized by Eli Lilly under the name of Zyprexa, is a representative example. 62 The carbon-14 radiosynthesis of this particular second-generation neuroleptic agent starts from a nickelcatalyzed cyanation of 3-bromo thiophene 74, according to a previously reported procedure. 63 Subsequent nitro group reduction, followed by Buchwald-Hartwig crosscoupling with 1-bromo-2-iodobenzene and N-methyl piperazine addition to the nitrile, afforded the key precursor [ 14 C]-76.…”

“…Tricyclic heterocycles are largely found in drugs with antipsychotic activity. Olanzapine, commercialized by Eli Lilly under the name of Zyprexa, is a representative example . The carbon‐14 radiosynthesis of this particular second‐generation neuroleptic agent starts from a nickel‐catalyzed cyanation of 3‐bromo thiophene 74 , according to a previously reported procedure .…”

Crystal structure determination of the antipsychotic drug of olanzapine form III

“…1), a thienobenzodiazepine derivative, is a second-generation antipsychotic mostly used for the treatment of schizophrenia and bipolar disorder due to its antagonist action for multiple neurotransmitter receptor sites. [1] Figure 1. Olanzapine molecular structure with the relative label scheme.…”

Reductive Condensation of a Nitro Group with Carboxylic Acids Promoted by Phosphorus(III) Compounds: A Short Route to 5H-Dibenzo[b,e][1,4]diazepin-11(10H)-ones

“…This can be easily transformed into 11-dialkylamino or other functionalized derivatives. [2][3][4][5][6] Moreover, dibenzodiazepin-11-ones themselves belong to the most prominent class of dibenzodiazepine derivatives amongst pharmaceutically important compounds ( Figure 1). They exhibit various biological activities such as neuroleptic, 7 antimicrobial and antitumor, 8 anticancer, 6,9 antidepressant, 10 antimicrobial, 11 antiallergic 12 and antihistaminic 12 activity.…”

“…According to one of them (Scheme 2, path a), the central, seven-membered amide ring is formed by condensation of a suitable pair of functions, the amine from one side and a carboxylderived group from the other side of the appropriate diarylamine, by means of various condensing agents and protocols. [2][3][4][5][6]14,15 As a rule, the starting materials are prepared by reducing the nitro group of an appropriate 2-nitrodiarylamine. When catalytic amination of a suitable chlorodiarylamine is used for this purpose, the reaction leads to the cyclic product without isolation of the amine intermediate.…”