Thioaryl sulfonamide hydroxamic acid compounds

Patent Thioaryl Sulfonamide Hydroxamic Acid Compounds 

Getman etal, US Patent 6,087,359 (July 11, 2000) Assignee Pharmacia Corporation 

Utility Proteinase Inhibitors for Treatment of Matrix Metalloproteinase 

To a solution of D-valine (54.6 mmol) dissolved in 62 ml water and 25 ml acetone was added triethylamine (117 mmol). The solution was cooled to 0°C and 4-fluorobenzenesulfonyl chloride (51.4 mmol) dissolved in 25 ml acetone added dropwise. After stirring at ambient temperature 20 hours, the solution was concentrated, the aqueous residue extracted twice with 50 ml toluene and then acidified with HCl to pH 1. The solution was extracted 3 times with 50 ml EtOAc, washed successively with 50 ml apiece of KHSO4, water, and brine, dried, concentrated, and triturated with hexane. The product was isolated in 89% yield. MS and elemental analysis data supplied. 

A solution of the product from Step 1 (29.1 mmol) in CH2Cl2/dioxane was treated with isobutylene in the presence of H2SO4 at room temperature at a pressure of 18psi. The reaction was quenched by adding 300 ml water containing NaHC03 (20 g). The mixture was extracted with EtOAc, washed, dried, and concentrated. The product was isolated in 73% yield after re-crystallization from diethyl ether/hexane. MS and elemental analysis data supplied. 

---

Patent Thioaryl Sulfonamide Hydroxamic Acid Compounds... 

---

See also in sourсe #XX -- [ , , , ]

---