Development of a New Synthetic Route of a Non-Peptide CCR5 Antagonist, TAK-779, for Large-Scale Preparation

✍ Scribed by Ikemoto, Tomomi; Ito, Tatsuya; Hashimoto, Hideo; Kawarasaki, Tadao; Nishiguchi, Atsuko; Mitsudera, Hiroyuki; Wakimasu, Mitsuhiro; Tomimatsu, Kiminori

• Book ID: 126216750
• Publisher: American Chemical Society
• Year: 2000
• Tongue: English
• Weight: 66 KB
• Volume: 4
• Category: Article
• ISSN: 1083-6160
• DOI: 10.1021/op000074v

✦ Synopsis

A new large-scalable preparation of TAK-779 (1), a non-peptide CCR5 antagonist, has been developed. The route selection was focused on in the process research. The selective reduction of commercially available benzonitrile derivative (4) as the starting material with sodium bis(2-methoxyethoxy)aluminum hydride followed by the Wittig reaction, hydrogenation, and intramolecular acylation gave benzocycloheptanone (7) in good yield. The conversion of r,β-unsaturated carboxylic acid (8) led from 7 to benzyl alcohol (9) and shortened the number of steps using non-protected 4-aminobenzyl alcohol. The reductive alkylation of Me 2 NH and tetrahydro-4H-pyran-4-one (12) smoothly gave a tertiary amine (3). The coupling of 2 chlorinated 9, and 3 successfully led to an ammonium chloride (1). A new inexpensive preparation which did not require a chromatographic method was achieved.