Dimethyl Sulfoxide → 4-{5-Chloro-2-[(1,1-dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile

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Reaction Conditions

Reaction Steps

A dry round bottom flask under nitrogen was charged with oxalyl chloride (2M solution in methylene chloride (9.15 mL, 18.3 mmol) and methylene chloride (125 mL) and cooled to −78° C. Dimethylsulfoxide was added dropwise (2.6 mL, 36.6 mmol) and the mixture was stirred for 10 min. A solution of 4-{2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}benzonitrile (2.5 g, 9.2 mmol), prepared in step 1 of Example 82, in 10 mL of tetrahydrofuran was added and the mixture stirred for 30 min. Triethylamine (7.9 mL, 55 mmol) was added and the mixture was stirred for 20 min and then allowed to warm to 25° C. The mixture was then diluted with methylene chloride and washed with H2O, brine, dried over anhydrous MgSO4, filtered and concentrated. Flash chromatography (20% acetone in hexane) afforded 4-{5-chloro-2-[(1,1-dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile (0.60 g, 22%) as a yellow solid. HRMS: calcd for C14H12ClN3OS+H+, 306.04623; found (ESI, [M+H]+), 306.0453; Analytical HPLC: purity see MS. MS & UV are same at 210-370 nm; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min.

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