Preparation of 2-Heteroaryl-indolin-3-ones by Acid-Mediated Intramolecular Cyclization in Batch and Flow
Zeynep Saglam1, Shuyu Liu1, Yiding Chen1
1Process and Analytical Chemistry, Pharmaron UK Ltd., West Hill Innovation Park, Hertford Road, Hoddesdon EN11 9FH, U.K.
Abstract:
An intramolecular cyclization strategy to synthesize nitrogen-rich and biologically important 2-heteroaryl-indolin-3-ones has been developed in both batch and flow. Using high-throughput screening, citric acid in a dimethylformamide/water mixture was found to facilitate the reaction under batch conditions, which can tolerate substituted phenyl rings, quinolines, and naphthalenes with a variety of electronic and steric properties. The reaction was reoptimized for flow conditions using design of experiments, complementing the batch conditions for some substrates with greatly reduced reaction times.
More Related Videos
10:17Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
07:06Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid
Published on: November 15, 2017
Related Concept Videos
Cycloaddition Reactions: Overview
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Preparation of Alkynes: Alkylation Reaction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
