221242-70-2

Upstream product

• 98-09-9 benzenesulfonyl chloride 
• 88-17-5 2-(trifluoromethyl)benzenamine 
• 221242-67-7 4-hydroxy-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid methyl ester 
• 358-23-6 trifluoromethylsulfonic anhydride 
• 221242-51-9 2-(2-trifluoromethyl-phenylsulfamoyl)-benzoic acid methyl ester 
• 221242-55-3 2-[methoxycarbonylmethyl-(2-trifluoromethyl-phenyl)-sulfamoyl]-benzoic acid methyl ester 
• 81-08-3 2-sulfobenzoic acid cyclic anhydride 
• 6939-89-5 o-sulfobenzoic acid, monoammonium salt 
• 128-44-9 saccharin sodium salt 
• 86802-68-8 N-(2-(trifluoromethyl)phenyl)benzenesulfonamide 

Downstream Products

• 221242-73-5 4-(3,5-dimethoxy-phenyl)-2-(2-trifluoromethyl-phenyl)-1,1-dioxo-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid methyl ester 
• 221246-11-3 4-(3,5-Dimethyl-phenyl)-2-(2-trifluoromethyl-phenyl)-1,1-dioxo-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Development of a scalable process for CI-1034, an endothelin antagonist

A concise, convergent multikilogram synthesis of CI-1034 (1), a potent endothelin receptor antagonist, is described. A 15-step preparation from commercially available o-vanillin and benzenesulfonyl chloride employs a remarkably robust Suzuki coupling between a boronic acid and an aromatic sulfonate ester as the key synthetic step. A scalable route capable of producing multikilogram quantities of CI-1034 with no chromatographic steps is described in this contribution. Improvements to the process included using a 4-fluorobenzenesulfonate ester as a suitable substitute for the triflate group in the Suzuki reaction and the use of MgCl2 as a substitute for TiCl4 in a Dieckmann condensation to provide the benzothiazine dioxide core.

Certain benzothiazine dioxide endothelin antagonists and processes for their preparation

The instant invention is a series of benzothiazine dioxides, or a pharmaceutically acceptable salt thereof, which are potent endothelin A antagonists with profound in vitro activity, and improved syntheses for the Formula 1 The compounds are useful in treating elevated levels of endothelin, essential renovascular malignant and pulmonary hypertension, cerebral infarction, cerebral ischemia, congestive heart failure, and subarachnoid hemorrhage.