【结 构 式】 |
【药物名称】UR-7247 【化学名称】3-Isopropyl-1-propyl-5-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-pyrazole-4-carboxylic acid 【CA登记号】177847-28-8 【 分 子 式 】C24H26N6O2 【 分 子 量 】430.51382 |
【开发单位】Uriach (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Angiotensin AT1 Antagonists |
合成路线1
Acid chloride (II) (prepared from 4-bromophenylacetic acid (I) and SOCl2), was condensed with ethyl isobutyrylacetate (III) in the presence of NaH in toluene to yield diketoester (IV). Further reaction of (IV) with hydrazine monohydrate in AcOH gave pyrazole (V). The subsequent N-alkylation of (V) with propyl iodide and NaH provided a 3:1 mixture of regioisomers (VI) and (VII), which were separated by silica gel chromatography. The major isomer (VI) was coupled with arylboronic acid (VIII) in the presence of CsF and Pd(PPh3)4 to provide biphenyl compound (IX). The title compound was then obtained by simultaneous cleavage of the ethyl ester and the N-trityl group on heating with hydroethanolic KOH.
【1】 Almansa, C.; Gonzales, C.; Torres, M.C.; Carceller, E.; Bartroli, J. (J. Uriach & Cia., SA); New pyrazole derivs. as angiotensin II antagonists. EP 0721454; ES 2105939; JP 1997504804; WO 9604273 . |
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) | 14247 | 2-(4-Bromophenyl)acetic acid; p-Bromophenylacetic acid; 4-Bromophenylacetic acid | 1878-68-8 | C8H7BrO2 | 详情 | 详情 |
(II) | 19407 | 2-(4-bromophenyl)acetyl chloride | C8H6BrClO | 详情 | 详情 | |
(III) | 19408 | ethyl 4-methyl-3-oxopentanoate | 7152-15-0 | C8H14O3 | 详情 | 详情 |
(IV) | 19409 | ethyl 2-[2-(4-bromophenyl)acetyl]-4-methyl-3-oxopentanoate | C16H19BrO4 | 详情 | 详情 | |
(V) | 19410 | ethyl 5-(4-bromobenzyl)-3-isopropyl-1H-pyrazole-4-carboxylate | C16H19BrN2O2 | 详情 | 详情 | |
(VI) | 19411 | ethyl 5-(4-bromobenzyl)-3-isopropyl-1-propyl-1H-pyrazole-4-carboxylate | C19H25BrN2O2 | 详情 | 详情 | |
(VII) | 19412 | ethyl 3-(4-bromobenzyl)-5-isopropyl-1-propyl-1H-pyrazole-4-carboxylate | C19H25BrN2O2 | 详情 | 详情 | |
(VIII) | 19413 | 2-(1-trityl-1H-1,2,3,4-tetraazol-5-yl)phenylboronic acid | C26H21BN4O2 | 详情 | 详情 | |
(IX) | 19414 | ethyl 3-isopropyl-1-propyl-5-[[2'-(1-trityl-1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-pyrazole-4-carboxylate | C45H44N6O2 | 详情 | 详情 |