Dimethyl sulfate is a typical genotoxic substance commonly used as a methylation reagent in drug synthesis. Compared with halogenated alkane methylation reagents, it has a faster reaction rate and fewer by-products. The reaction types are summarized in the following table:

Example 1: Synthesis of Rotigotine

Rotigotine is suitable for the treatment of early and advanced Parkinson's disease. It was developed by Schwartz, a German company and approved for market by the US FDA in 2007. The synthesis of rotigotine used dimethyl sulfate for O-methylation reaction, followed by multi-step conversion to synthesize the target product.

Example 2: Synthesis of Relytoline

The synthesis process of the antiepileptic drug Relytoline uses dimethyl sulfate as a methylation reagent to complete the N-methylation reaction.

Example 3: Synthesis of Avimopan

Avimopan is jointly developed by GlaxoSmithKline and Adolo, and was approved by the US FDA in May 2008 for early recovery of gastrointestinal function in patients after intestinal resection surgery. In the synthesis process of Avimopan, butyl lithium and dimethyl sulfate are used to treat styrene derivatives, completing the C-methylation reaction.

Example 4: Synthesis of cimetidine

Cimetidine is the first heavyweight drug invented by Nobel laureate James Black. It is a selective H2 receptor antagonist used for the treatment of peptic ulcers. It uses dimethyl sulfate for S-alkylation reaction in its synthesis process.

Example 5: Synthesis of Chlorpheniramine Fumarate

Fumarate chloramphenicol is a representative second-generation H1 receptor antagonist used clinically to treat various allergic diseases caused by histamine, and is currently recognized as one of the world's most effective antihistamines. In its synthesis process, dimethyl sulfate is used for quaternization reaction, followed by the introduction of a cyanide synthesis strategy.

Example 6: Synthesis of Neostigmine Methanesulfate

Methylsulfamethoxazole is a commonly used anisotropic acetylcholinesterase drug, commonly used in various types of flaccid paralysis, muscle and neurological disorders in internal medicine, gynecology, and ophthalmology. In the final step of its synthesis, dimethyl sulfate is used for N-methylation to form quaternary ammonium salts.