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【结 构 式】

【药物名称】ABT-963

【化学名称】2-(3,4-Difluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

【CA登记号】266320-83-6, 444617-70-3 (deleted CAS)

【 分 子 式 】C22H22F2N2O5S

【 分 子 量 】464.49184

【开发单位】Abbott (Originator)

【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Antiarthritic Drugs, Osteoarthritis, Treatment of, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Cyclooxygenase-2 Inhibitors

合成路线1

Diazotization of 3,4-difluoroaniline (I), followed by reduction with SnCl2 gives rise to hydrazine (II). This is then condensed with mucobromic acid (III) in refluxing AcOH to produce the pyridazinone (IV). Selective displacement of the 4-bromo of (IV) with the sodium alkoxide of 3-methyl-1,3-butanediol (V) yields ether (VI). 4-(Methylsulfanyl)benzeneboronic acid (VIII) is prepared by metalation of 4-bromothioanisole (VII) with butyl lithium, followed by reaction with trimethyl borate, and aqueous work-up. Suzuki coupling of boronic acid (VIII) with bromopyridazinone (VI) furnishes the 5-(methylsufanylphenyl)pyridazinone (IX). Finally, the sulfide group of (IX) is oxidized to the target sulfone by using peracetic acid in cold dichloromethane.

1 Stewart, A.O.; Black, L.A.; Basha, A.; Patel, M.V.; Kolasa, T.; Coghlan, M.J.; Liu, H.; Kort, M.E.; McCarty, C.M.; Rohde, J.J. (Abbott Laboratories Inc.); Prostaglandin endoperoxide H synthase biosynthesis inhibitors. EP 1124804; JP 2003512292; WO 0024719 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 13451 3,4-Difluoroaniline; 3,4-Difluorophenylamine 3863-11-4 C6H5F2N 详情 详情
(II) 61025 1-(3,4-difluorophenyl)hydrazine C6H6F2N2 详情 详情
(III) 22280 (Z)-2,3-dibromo-4-oxo-2-butenoic acid 21577-50-4 C4H2Br2O3 详情 详情
(IV) 61026 4,5-dibromo-2-(3,4-difluorophenyl)-3(2H)-pyridazinone C10H4Br2F2N2O 详情 详情
(V) 61027 3-methyl-1,3-butanediol C5H12O2 详情 详情
(VI) 61028 5-bromo-2-(3,4-difluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-3(2H)-pyridazinone C15H15BrF2N2O3 详情 详情
(VII) 19266 4-bromophenyl methyl sulfide; 1-bromo-4-(methylsulfanyl)benzene 104-95-0 C7H7BrS 详情 详情
(VIII) 18561 4-(methylsulfanyl)phenylboronic acid 98546-51-1 C7H9BO2S 详情 详情
(IX) 61029 2-(3,4-difluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-[4-(methylsulfanyl)phenyl]-3(2H)-pyridazinone C22H22F2N2O3S 详情 详情
Extended Information