Synthesis of 2,3‐Diaryl‐3H‐pyrrolo[2,3‐c]pyridin‐3‐ol Derivatives by the Reaction of Aryl(3‐isocyanopyridin‐4‐yl)methanones with Aryl Grignard Reagents

Abstract

The reaction of aryl(3-isocyanopyridin-4-yl)methanones 1, easily prepared from commercially available pyridin-3-amine, with aryl Grignard reagents gave, after aqueous workup, 2,3-diaryl-3H-pyrrolo[2,3-c]pyridin-3-ols 2. These rather unstable alcohols were O-acylated with Ac 2 O in pyridine in the presence of a catalytic amount of 4-(dimethylamino)pyridine (DMAP) to afford the corresponding 2,3-diaryl-3H-pyrrolo[2,3-c]pyridin-3-yl acetates 3 in relatively good yields.Introduction. -As part of our program to explore the potential of the reactions of ortho-functionalized phenyl isocyanides with organometals for heterocycle synthesis [1], we have recently demonstrated that 2-isocyanophenyl ketones can be converted into 2,3-disubstituted 3H-indol-3-ols in generally good yields on treatment with Grignard reagents [1e]. As an extension of this synthesis, we envisioned that a synthesis of 2,3-disubstituted 3H-pyrrolo[2,3-c]pyridin-3-ols could be accomplished by reacting 3-isocyanopyridin-4-yl ketones with Grignard reagents. Here, we report the results of such a study. The investigation has indicated that the reactions of aryl(3-isocyanopyridin-4-yl)methanones 1 with aryl Grignard reagents provide a convenient synthetic approach to 2,3-diaryl-3H-pyrrolo[2,3-c]pyridin-3-ol derivatives 3. Due to instability of these alcohols during purification procedures, they were isolated as O-acetylated derivatives. There have been so far no reports on the synthesis of this heterocyclic skeleton, 3H-pyrrolo[2,3-c]pyridin-3-ol.

A Novel Synthesis of Quinazolines by Cyclization of 1‐(2‐Isocyanophenyl)alkylideneamines Generated by the Treatment of 2‐(1‐Azidoalkyl)phenyl Isocyanides with NaH

“…2-(Aminophenyl)(4-chlorophenyl)methanone [10], (2-amino-5-chlorophenyl)(4-methylphenyl)methanone [11], (2-amino-5-methoxyphenyl)phenylmethanone [12], N-[2-ethanoylphenyl]formamide [13], N-(2-benzoylphenyl)formamide [14], N-[3-chloro-6-(chloromethyl)phenyl]formamide [7], N-[2-(azido-Scheme 2 methyl)phenyl]formamide (1a) [6], N-(4-benzoylpyridin-3-yl)formamide [8], and N-[4-(4-chlorobenzoyl)pyridin-3-yl]formamide [9] were prepared according to the reported procedures. All other chemicals used in this study were commercially available.…”

Synthesis of 2‐Aryl‐2,3‐dihydro‐1,8‐naphthyridin‐4(1H)‐ones by Deprotective Cyclization of N‐{3‐[(2E)‐3‐Arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides in Water

“…Therefore, we embarked on the research on developing a novel and facile method for the preparation of 2,3‐dihydro‐1,8‐naphthyridin‐4(1 H )‐one derivatives. We previously reported that N ‐lithio‐ N ‐(4‐lithiopyridin‐3‐yl)‐2,2‐dimethylpropanamide reacted with N ‐methoxy‐ N ‐methylbenzamides to give N ‐(4‐aroylpyridin‐3‐yl)‐2,2‐dimethylpropanamide, from which 1,7‐naphthyridine and 3‐aryl‐3 H ‐pyrrolo[2,3‐ c ]pyridin‐3‐ol derivatives could be prepared. We envisioned the possibility of preparing N ‐{3‐[(2 E )‐3‐arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides 3 from N ‐lithio‐ N ‐(3‐lithiopyridin‐2‐yl)‐2,2‐dimethylpropanamide via reactions with (2 E )‐3‐arylprop‐2‐enals, followed by oxidation.…”