【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 |