methyl 4-[5-(1,5-diisopropyl-1H-pyrazol-3-yl)-1H-pyrrol-2-yl]benzoate -Drug Synthesis Database

【结构式】

【分子编号】42306

【品名】methyl 4-[5-(1,5-diisopropyl-1H-pyrazol-3-yl)-1H-pyrrol-2-yl]benzoate

【CA登记号】

【分子式】C₂₁H₂₅N₃O₂

【分子量】351.44852

【元素组成】C 71.77% H 7.17% N 11.96% O 9.1%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(IV)

The cyclization of 3-(2,6-dichloro-5-fluoropyridin-3-yl)-3-oxopropionic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid ethyl ester (III), which is oxidized with MCPBA in dichloromethane, yielding the sulfinyl derivative (IV). The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazolonaphthyridine (V), which is finally condensed with piperazine in pyridine to furnish the target compound.

参考文献中间体

合成目标

【1】 Aquilar-Bryan, L.; Bryan, J.; Boyd, A.E. III; et al.; Sulfonylurea signal transduction. Recent Prog Horm Res 1991, 47, 299-317.
【2】 Chu, D.T.W.; Isothiazoloquinolones: Antibacterial and antineoplastic agents. Drugs Fut 1992, 17, 12, 1101.

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)	15228	ethyl 3-(2,6-dichloro-5-fluoro-3-pyridinyl)-3-oxopropanoate		C₁₀H₈Cl₂FNO₃	详情	详情
(II)	43201	1-[[chloro(cyclopropylimino)methyl]sulfanyl]benzene		C₁₀H₁₀ClNS	详情	详情
(III)	43205	ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro[1,8]naphthyridine-3-carboxylate		C₂₀H₁₆ClFN₂O₃S	详情	详情
(IV)	42306	methyl 4-[5-(1,5-diisopropyl-1H-pyrazol-3-yl)-1H-pyrrol-2-yl]benzoate		C₂₁H₂₅N₃O₂	详情	详情
(V)	43027	tert-butyl (1S)-1-isobutyl-3-methyl-2-oxo-3-butenylcarbamate		C₁₄H₂₅NO₃	详情	详情
(VI)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

Condensation of 3-methyl-2-butanone (I) with methyl 2-methoxyacetate (II) by means of sodium in toluene gave diketone (III). Pyrazole (IV) was prepared by treatment of diketone (III) with hydrazine. Subsequent alkylation of pyrazole (IV) with isopropyl iodide in the presence of sodium hydride provided a mixture of N-alkylated regioisomers (V) and (VI). The desired minor isomer (V) was demethylated with BBr3 and the resulting alcohol (VII) was oxidized to aldehyde (VIII) using manganese dioxide. Addition of vinylmagnesium bromide to the formyl group of (VIII) produced allylic alcohol (IX), which was further oxidized to ketone (X) with MnO2. The benzoin-type condensation of unsaturated ketone (X) with aldehyde (XI) in the presence of 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride furnished the 1,4-diketone (XII). Cyclization of (XII) to pyrrole (XIII) was carried out by treatment with ammonium acetate in refluxing MeOH. Finally, ester hydrolysis by means of NaOH gave rise to the corresponding carboxylic acid.

参考文献中间体

合成目标

【1】 Yamauchi, T.; Tokuhara, N.; Yoshimura, H.; Nagai, M.; Hida, T.; Tai, K.; Hibi, S.; Kikuchi, K.; Novel retinoic acid receptor alpha agonists: Syntheses and evaluation of pyrazole derivatives. Bioorg Med Chem Lett 2000, 10, 7, 619.

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)	26143	3-methyl-2-butanone	563-80-4	C₅H₁₀O	详情	详情
(II)	19100	methyl 2-methoxyacetate	6290-49-9	C₄H₈O₃	详情	详情
(III)	42297	1-methoxy-5-methyl-2,4-hexanedione		C₈H₁₄O₃	详情	详情
(IV)	42298	(3-isopropyl-1H-pyrazol-5-yl)methyl methyl ether; 3-isopropyl-5-(methoxymethyl)-1H-pyrazole		C₈H₁₄N₂O	详情	详情
(V)	42299	1,5-diisopropyl-3-(methoxymethyl)-1H-pyrazole; (1,5-diisopropyl-1H-pyrazol-3-yl)methyl methyl ether		C₁₁H₂₀N₂O	详情	详情
(VI)	42300	1,3-diisopropyl-5-(methoxymethyl)-1H-pyrazole; (1,3-diisopropyl-1H-pyrazol-5-yl)methyl methyl ether		C₁₁H₂₀N₂O	详情	详情
(VII)	42301	(1,5-diisopropyl-1H-pyrazol-3-yl)methanol		C₁₀H₁₈N₂O	详情	详情
(VIII)	42302	1,5-diisopropyl-1H-pyrazole-3-carbaldehyde		C₁₀H₁₆N₂O	详情	详情
(IX)	42303	1-(1,5-diisopropyl-1H-pyrazol-3-yl)-2-propen-1-ol		C₁₂H₂₀N₂O	详情	详情
(X)	42304	1-(1,5-diisopropyl-1H-pyrazol-3-yl)-2-propen-1-one		C₁₂H₁₈N₂O	详情	详情
(XI)	10170	methyl 4-formylbenzoate	1571-08-0	C₉H₈O₃	详情	详情
(XII)	42305	methyl 4-[4-(1,5-diisopropyl-1H-pyrazol-3-yl)-4-oxobutanoyl]benzoate		C₂₁H₂₆N₂O₄	详情	详情
(XIII)	42306	methyl 4-[5-(1,5-diisopropyl-1H-pyrazol-3-yl)-1H-pyrrol-2-yl]benzoate		C₂₁H₂₅N₃O₂	详情	详情

Extended Information