The Production Process of Hexahydro-1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyrimidinyl]-1H-azepine

The production process of Hexahydro-1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyrimidinyl]-1H-azepine, also known as BMS-986039, is a complex and multi-step process that involves several chemical reactions and purification steps.
The final product is an anti-inflammatory drug that is used to treat conditions such as rheumatoid arthritis and asthma.

The production process of Hexahydro-1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyrimidinyl]-1H-azepine can be divided into several stages, including the synthesis of the starting materials, the primary reaction steps, and the purification and isolation of the final product.

Synthesis of starting materials

The synthesis of starting materials is the first step in the production process of Hexahydro-1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyrimidinyl]-1H-azepine.
The starting materials used in this process include 2-pyrimidinecarboxylic acid, 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2,4-disulfonic acid, methyl 1,3-oxazabutan-3-ylcarboxylate, and hexamethylenetetramine.
These materials can be synthesized using various chemical reactions and purification methods, such as hydrolysis, esterification, and condensation reactions.

Primary reaction steps

The primary reaction steps in the production process of Hexahydro-1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyrimidinyl]-1H-azepine include the synthesis of the dioxaborolane intermediate, the synthesis of the target compound, and the reduction of the target compound.

The dioxaborolane intermediate is synthesized by reacting 2-pyrimidinecarboxylic acid and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2,4-disulfonic acid in the presence of a base, such as sodium hydroxide.
This reaction results in the formation of a dioxaborolane intermediate, which is then used in the next step of the synthesis.

The target compound is synthesized by reacting the dioxaborolane intermediate with methyl 1,3-oxazabutan-3-ylcarboxylate and hexamethylenetetramine in the presence of a catalyst, such as palladium on barium carbonate.
This reaction results in the formation of the target compound, which is then reduced to form the final product.

Purification and isolation

The final step in the production process of Hexahydro-1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyrimidinyl]-1H-azepine is the purification and isolation of the final product.
This step involves several methods, such as crystallization, chromatography, and recrystallization, to remove any impurities and to obtain a pure sample of the final product.

The overall production process of Hexahydro-1-[