Efforts toward a convenient and scalable process for the synthesis of a novel CXCR antagonist 1 are described, with a specific focus on a chiral key intermediate. Two generations of a racemic route have been developed for short-term deliveries, and a stereoselective process has been devised for longer term plans. Key steps involved an enzymatic resolution of racemic tetrahydrothiophene-2-carboxylic acid to install the (2R) stereocenter, the mild and efficient preparation of a sterically hindered sulfinimine under a nitrogen flow, and its stereoselective reduction to set up the (1S) amine stereocenter. The process has been scaled-up to multikilogram scale for the racemic approach, and the stereoselective route was demonstrated on multigram scale.

中文翻译：

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新型CXCR拮抗剂的早期开发规模扩大：重点研究关键中间体的外消旋和立体选择性途径

描述了对合成新型CXCR拮抗剂1的方便且可扩展的方法的努力，特别着重于手性关键中间体。已经开发出两代外消旋路线用于短期交付，并且已经为长期计划设计了立体选择过程。关键步骤涉及外消旋四氢噻吩-2-羧酸的酶促拆分，以建立（2 R）立体中心，在氮气流下温和有效地制备位阻亚氨嘧啶，及其立体选择性还原以建立（1 S）胺立体中心。对于外消旋方法，该过程已扩大到几千克规模，而立体选择性路线已在多克规模上得到证明。