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    • 22. 发明公开
    • 신규한 치환된 할로아렌 화합물의 제조 방법
    • 新型取代的HALOARENE化合物的制备
    • KR1020070028551A
    • 2007-03-12
    • KR1020077001274
    • 2005-07-07
    • 화이자 프로덕츠 인크.
    • 루더포드,제니퍼,리아호킨스,조엘,마이클
    • C07D213/61C07D213/28
    • C07C29/40C07C2601/08C07C2601/14C07D213/61C07C33/46C07C33/44C07C31/125
    • This invention relates to a new process for the preparation of novel substituted haloarene compounds of the formula I or IV: respectively, wherein R1, R2, R3, R4, R5, X, and Y are as defined herein, that comprises a novel and efficient selective mono-lithiation of a dihaloarene of the formula II or V: respectively, by an organo-lithium compound in the presence of a carbonyl reactant of the formula III: wherein R1 and R2 are as defined herein. In the process of the instant invention, the newly formed lithiated haloarene is sequentially quenched in situ by the carbonyl reactant to form said substituted haloarene. The process is suitable for batch or continuous flow systems. The substituted haloarenes produced by the process of the present invention are useful intermediates in the preparation of N-aryl or N-heteroaryl substituted pharmaceutically active compounds that include selective antagonists, inverse agonists and partial agonists of serotonin 1 (5-HT1) receptors useful in treating or preventing depression, anxiety, obsessive compulsive disorder (OCD) and other disorders for which a 5-HT1 agonist or antagonist is indicated. ® KIPO & WIPO 2007
    • 本发明涉及分别制备式I或IV的新的取代的卤代芳烃化合物的新方法:其中R1,R2,R3,R4,R5,X和Y如本文所定义,其包含新颖有效的 在式III的羰基反应物存在下,分别用有机锂化合物选择性地单取式II或V的二卤代芳烃:其中R1和R2如本文所定义。 在本发明的方法中,新形成的锂化卤代芳烃通过羰基反应物原位连续淬灭以形成所述取代的卤代芳烃。 该方法适用于批量或连续流动系统。 通过本发明方法制备的取代的卤代芳烃是制备N-芳基或N-杂芳基取代的药物活性化合物的有用中间体,其包括选择性拮抗剂,反激动剂和部分激动剂,其可用于5-羟色胺1(5-HT1)受体 治疗或预防抑郁,焦虑,强迫症(OCD)以及其中指示5-HT1激动剂或拮抗剂的其它病症。 ®KIPO&WIPO 2007