A New Industrial Process for 10-Methoxyiminostilbene: Key Intermediate for the Synthesis of Oxcarbazepine

Abstract

A new industrial process, involving only two isolation and drying steps, for 10-methoxyiminostilbene (MISB), an advance intermediate of widely prescribed antiepileptic drug, oxcarbazepine, has been developed. A salient feature of this process is the novel use of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) to afford bromohydrin methyl ether from N-acetyliminostilbene. The byproducts of this process namely acetic acid, 5,5-dimethylhydantoin and Et 3 N • HBr are recyclable as well as nontoxic. This process is amenable for the large-scale production of MISB.

Synthesis of Pyrimidine‐Fused Benzazepines from 5‐Allyl‐4,6‐dichloropyrimidines

“…[4][5][6][7][8][9][10] Additionally, imipramine has also been used as a template for development of anticancer agents. [12][13][14][15][16][17][18][19][20][21][22][23][24][25] In contrast, DBAs' 1,3-diaza analogues -namely benzo [b]pyrimido [5,4-f]azepines (BPAs), also containing a privileged 6-7-6 ring system -are a less investigated family of compounds, due, probably, to the lack of applicable methods for their synthesis. [12][13][14][15][16][17][18][19][20][21][22][23][24][25] In contrast, DBAs' 1,3-diaza analogues -namely benzo [b]pyrimido [5,4-f]azepines (BPAs), also containing a privileged 6-7-6 ring system -are a less investigated family of compounds, due, probably, to the lack of applicable methods for their synthesis.…”

5H-Dibenz[b,f]azepine based pyrazole sulphonamides: A privileged platform for probing the antimicrobial and antioxidative properties

“…The seven-membered ring 5H-dibenz[b,f]azepine nucleus (1) is a pharmaceutically important structure and constitutes the key subunit in tricyclic antidepressant drug substances such as carbamazepine (1a) and oxcarbazepine (1b) (Figure 1) [4]. These anticonvulsant and mood stabilizing drugs are primarily used for the treatment of epilepsy, bipolar disorder [5][6][7], trigeminal neuralgia [8], and other neurological disorders [9].…”

Cobalt‐Catalyzed Reductive Dimethylcyclopropanation of 1,3‐Dienes

“…Notably, previous attempts to cyclopropanate this substrate under Simmons–Smith conditions (CH 2 I 2 + Zn/Cu) only yielded the product of methylene insertion into the N–H bond. [22] One-step derivatization of 37 using chlorosulfonyl isocyanate [23] yielded a dimethylcyclopropane-containing analogue ( 38 ) of carbamazepine, [21b] which is used as a treatment for epilepsy and neuropathic pain.…”

“…Tricyclic antidepressants (TCAs) are a class of compounds that commonly contain a dibenzazepine. [21] Parent 5H-dibenz[b,f]azepine ( 36 ), bearing an unprotected N -H group, could be directly dimethylcyclopropanated to provide 37 in 96% yield. Notably, previous attempts to cyclopropanate this substrate under Simmons–Smith conditions (CH 2 I 2 + Zn/Cu) only yielded the product of methylene insertion into the N–H bond.…”