An improved synthesis of 1,3-dihydro-1-methyl-5-phenyl-2H-pyrido[3,4-e]-1,4-diazepin-2-one via ortho-directed lithiation of 3-tert-butyl and 3-tert-butoxycarbonylaminopyridine

Abstract

. Can. J. Chem. 65, 1158Chem. 65, (1987. The ortho-directed lithiation of 3-tert-butyl-or 3-tert-butoxycarbonylaminopyridines (3) with alkyllithiums and reaction with N,N-diethylbenzamide followed by acid hydrolysis gave 3-amino-4-benzoylpyridine (6) in good yield. Reaction of BTBO with the glycine derivatives 70, b and then reaction with 6 afforded 3-alkoxycarbonylaminomethylcarbonylamino-4-benzoylpyridines 8a, b. Acid-catalyzed hydrolysis and cyclization of 80, b yielded 9, which on methylation gave 1,3-dihydrol-methyl-5-phenyl-2H-pyrido[3,4-e]-1,4-diazepin-2-one (10) in 36% overall yield from 30. CHARLES Y. FIAKPU~ et EDWARD E. KNAUS. Can. J. Chem. 65, 1 158 (1987). La lithiation en position ortho des tert-butyl-ou tert-butoxycarbonylamino-3 pyridines (3) par les alkyllithiens ou leur rkaction avec du N,N-dikthylbenzamide, suivie d'une hydrolyse acide, conduisent a l'amino-3 benzoyl-4 pyridine (6) avec de bons rendements. La reaction du BTBO avec les dkrivts 70, b de la glycine, suivie d'une rkaction avec le compost 6, conduit aux alkoxycarbonylaminomkthylcarbonylamino-3 benzoyl-4 pyridines (8a, b). L'hydrolyse acido-catalyske des composks 8a, b, suivie d'une cyclisation, conduit au composk 9 qui, par mkthylation, fournit ladihydro-1,3 mkthyl-1 phknyl-5 2H-pyrido [3,4-e] diazkpine-1,4 one-2 (lo), avec un rendement global de 36% a partir du composk 30.

Development of 1,4-benzodiazepine cholecystokinin type B antagonists

“…)carbonyl]amino)-2,3-dihydro-2-oxo-5-phenyl-lH-l,4-benzodiazepine-l-acetic Acid (14). The ester 9 (550 mg, 1.12 mmol) was added to a mixture of 10 mL of THF and 1 N sodium hydroxide solution (4 mL) at 23 °C.…”

Towards New Tricyclic Motifs: Intramolecular C–H Arylation as the Key Step in a Formal [3+3] Cyclocondensation Strategy

“…Unfortunately, preliminary research in our group quickly led us to observe that the problematic preparation of pyridodiazepinedione (PZD) 11 as the TRALEC reaction precursor was undermining the feasibility of this synthetic route (Scheme 1). [8] Based on a recent database search, we can conclude that this statement about the synthetically challenging pyridodiazepines is still remarkably up to date. Using a microwave-assisted TRALEC reaction to convert PZD 11 into ONO 12, the overall yield of the synthetic sequence was just 3 %.…”

“…been studied clinically, as their syntheses usually require aminopyridinecarboxylic acid precursors, and give low overall yields. [8] Based on a recent database search, we can conclude that this statement about the synthetically challenging pyridodiazepines is still remarkably up to date.…”

The First Enantiomerically Pure [n]Triangulanes and Analogues: σ-[n]Helicenes with Remarkable Features

“…It will also be quite interesting to investigate the Raman optical activities (ROA) of the whole series of enantiomerically pure methylene[n-1]triangulanes and [n]triangulanes, since the ROA of (M)-(À)- [4]triangulane (M)-(À)-3 has been shown to disclose spectacular effects with D values close to 0.5 % in the 900 cm À1 region. [36] Experimental Section General aspects: Racemic bicyclopropylidenecarboxylic acid rac-12, [12] racemic exo-dispiro[2.0.2.1]heptane-1-carboxylic acid rac-13, [13] racemic anti-rac-1-(tetrahydropyranyloxymethyl)-4-methylenespiropentane, [37] racemic 1-methylenedispiro[2.0.2.1]heptane (rac-28), [38] racemic [4]triangulane (rac-trispiro[2.0.0.2.1.1]nonane rac-3), [38] enantiomerically pure anti-(4-methylenespiropentyl)methanols (1R,3S)-and (1S,3R)-18, [18] (6), [39] and (N-tert-butoxycarbonyl)glycine (7) [40] were prepared according to the previously published procedures. The acid rac-12 was purified by column chromatography on silica gel (eluent hexane/Et 2 O 3:2) followed by recrystallization from hexane (rac-12: m.p.…”