【结 构 式】 |
【分子编号】61029 【品名】2-(3,4-difluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-[4-(methylsulfanyl)phenyl]-3(2H)-pyridazinone 【CA登记号】 |
【 分 子 式 】C22H22F2N2O3S 【 分 子 量 】432.4911664 【元素组成】C 61.1% H 5.13% F 8.79% N 6.48% O 11.1% S 7.41% |
合成路线1
该中间体在本合成路线中的序号:(IX)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 |