Synthesis of [3,5‐dichlorobenzenesulfonamide‐U‐¹⁴C)] labeled VLA‐4 antagonists

Abstract

SummaryRadiolabeled tracers were required for the development of a series of VLA-4 antagonists. A method to synthesize [U-14 C]3,5-dichlorobenzenesulfonyl chloride was developed. From this key intermediate, various tracers were prepared in high yield.

Synthesis of typical sulfonamide antibiotics with [14C]- and [13C]-labelling on phenyl ring for environmental studies

“…We performed the acetylation in aqueous solution with addition of K 2 CO 3 to improve nucleophilic activity of aniline (1a), resulting in acetylaniline (2a) in a good yield of 90.0%. The method with less procedures was more convenient than the previous report [29].…”

“…Chlorosulfonation of 2a with ClSO 3 H generated the key intermediate 3a, which can be used as precursor to synthesize a variety of [ 14 C]-SAs with labeling on the phenyl ring by reacting with different amino heterocycles and subsequent alkaline hydrolysis. In a previous study, the synthesis of 3a with 1.1 g of 2a, and a high molar ratio of ClSO 3 H was used together with 2a (18:1) to obtain 3a the form of white solid after crystallizing in water [29]. However, the use of overdose of ClSO 3 H was not appliable to the synthesis of 3a milligram scale (12 mg of 2a) in our study, because the hot H 2 SO 4 , derived from hydrolysis of the excess ClSO 3 H in water, could decompose 3a, resulting in a low yield of 3a.…”

Synthesis of typical sulfonamide antibiotics with [14C]- and [13C]-labeling on the phenyl ring for use in environmental studies

“…The acetylation was performed in aqueous solution, and K 2 CO 3 was added to improve nucleophilic activity of aniline ( 1a ), resulting in acetylaniline ( 2a ), with a good yield of 90.0%. Our preparation of 2a with fewer procedures was more convenient than the previously reported method [ 29 ].…”

“…Chlorosulfonation of 2a with ClSO 3 H generated the key intermediate 3a , a precursor in the synthesis of a variety of [ 14 C]-SAs labeled on the phenyl ring via reactions with different amino heterocycles and subsequent alkaline hydrolysis. In a previous study, 1.1 g of 2a at a high molar ratio of ClSO 3 H to 2a (18:1) was used to obtain 3a , which formed a white solid after crystallization in water [ 29 ]. However, this method of using a high volume of ClSO 3 H cannot be applied to synthesize 3a at milligram scale (12 mg of 2a ), because the hot H 2 SO 4 , derived from the hydrolysis of excess ClSO 3 H in water, causes the decomposition of 3a , resulting in a very low yield.…”