ethyl 5-(4-bromobenzyl)-3-isopropyl-1H-pyrazole-4-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】19410

【品名】ethyl 5-(4-bromobenzyl)-3-isopropyl-1H-pyrazole-4-carboxylate

【CA登记号】

【分子式】C₁₆H₁₉BrN₂O₂

【分子量】351.24314

【元素组成】C 54.71% H 5.45% Br 22.75% N 7.98% O 9.11%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(V)

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.

参考文献中间体

合成目标

【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

Extended Information