The Synthetic Routes of (S,E)-4-(dimethylamino)-N-(4-oxo-7-((tetrahydrofuran-3-yl)oxy)-3,4-dihydroquinazolin-6-yl)but-2-enamide

Synthetic Route of (S,E)-4-(dimethylamino)-N-(4-oxo-7-((tetrahydrofuran-3-yl)oxy)-3,4-dihydroquinazolin-6-yl)but-2-enamide: An Overview of the Chemical Industry

Introduction

The synthesis of (S,E)-4-(dimethylamino)-N-(4-oxo-7-((tetrahydrofuran-3-yl)oxy)-3,4-dihydroquinazolin-6-yl)but-2-enamide is a complex and challenging process that involves several steps, including the synthesis of the tetrahydrofuran-3-yl ester, the condensation of the ester with the amino acid, the cyclization of the intermediate product, and the final deprotection of the amino group.

In this article, we will review the synthetic routes and methods used to synthesize (S,E)-4-(dimethylamino)-N-(4-oxo-7-((tetrahydrofuran-3-yl)oxy)-3,4-dihydroquinazolin-6-yl)but-2-enamide, which is an important compound in the field of medicine and pharmacology.

Synthetic Route 1: Via the Topfolding of the Tetrahydrofuran

The first synthetic route involves the topfolding of the tetrahydrofuran ring, which is a challenging and complex step.
The process involves the reaction of the tetrahydrofuran-3-yl ester with a strong acid, such as hydrochloric acid, in the presence of an alcohol, such as methanol or ethanol.
The reaction yields a mixture of the desired product and the corresponding alcohol, which must be separated from the reaction mixture.

Synthetic Route 2: Via the Condensation of the Tetrahydrofuran-3-yl Ester with the Amino Acid

The second synthetic route involves the condensation of the tetrahydrofuran-3-yl ester with the amino acid, which is reacted with the activated ester in the presence of a condensing agent, such as dicyclohexylcarbodiimide (DCC) or hydroxybenzotriazole (HOBT).
The reaction requires the presence of a solvent, such as dichloromethane or chloroform, and a base, such as pyridine or triethylamine.
The product is then isolated by chromatography or recrystallization.

Synthetic Route 3: Via the Cyclization of the Intermediate Product

The third synthetic route involves the cyclization of the intermediate product, which is formed by the condensation of the tetrahydrofuran-3-yl ester with the amino acid.
The process involves the reaction of the intermediate product with a strong acid, such as hydrochloric acid, in the presence of a water-soluble phase transfer catalyst, such as sodium hydroxide or potassium hydroxide.
The product is then isolated by filtration and washed with water.

Synthetic Route 4: Via the Final Deprotection of the Amino Group

The final synthetic route involves the deprotection of the amino group, which is protected by a tert-butyl group.
The process involves the reaction of the tert-butyl ester with a strong base, such as lithium hydroxide or sodium hydroxide, in the presence of a solvent, such as ether or THF.
The product is then isolated by filtration and washed with water.

Conclusion

The synthesis of (S,E)-4-(dimethylamino)-N-(4-oxo-7-((tetrahydrofuran-3-yl)oxy)-3,4-dihydroquinazolin-6-yl)