SB-272183, -Drug Synthesis Database

【结构式】

【药物名称】SB-272183

【化学名称】5-Chloro-6-(4-methylpiperazin-1-yl)-N-[4-(4-pyridyl)naphthalen-1-yl]indoline-1-carboxamide

【CA登记号】216058-27-4

【分子式】C₂₉H₂₈ClN₅O

【分子量】498.03241

【开发单位】GlaxoSmithKline (Originator)

【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, 5-HT1A Antagonists, 5-HT1B Antagonists, 5-HT1D Antagonists

合成路线1 合成路线2

合成路线1

Suzuki coupling of 4-bromonaphth-1-ylamine (I) with 4-pyridylboronic acid (II) furnished 4-(pyridyl)-1-naphthylamine (III), which was further converted into isocyanate (IV) by treatment with triphosgene.

参考文献中间体

【1】 Evans, M.; Gaster, L.M.; Gordon, l.; et al.; Mixed 5-HT1A/1B/1D receptor antagonists as novel antidepressants. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PB-77.
【2】 Gaster, L.M.; Rami, H.K.; Wyman, P.A. (SmithKline Beecham plc); Indole derivs. having combined 5HT1A, 5HT1B and 5HT1D receptor antagonist activity. EP 0975593; WO 9850358 .

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)	44706	4-bromo-1-naphthalenamine; 4-bromo-1-naphthylamine		C₁₀H₈BrN	详情	详情
(II)	44707	4-pyridinylboronic acid	1692-15-5	C₅H₆BNO₂	详情	详情
(III)	44708	4-(4-pyridinyl)-1-naphthalenamine; 4-(4-pyridinyl)-1-naphthylamine		C₁₅H₁₂N₂	详情	详情
(IV)	44709	4-(4-pyridinyl)-1-naphthyl isocyanate; 4-(4-isocyanato-1-naphthyl)pyridine		C₁₆H₁₀N₂O	详情	详情

合成路线2

Catalytic hydrogenation of 1-acetyl-6-nitroindoline (V) afforded amine (VI). Condensation of (VI) with mechlorethamine hydrochloride (VIII) in the presence of K2CO3 in refluxing n-butanol produced piperazinylindoline (X). Alternatively, intermediate (X) was obtained by Sandmeyer reaction of amine (VI) in the presence of CuBr, followed by condensation of the resulting bromide (VII) with N-methylpiperazine (IX). Chlorination of (X) with N-chlorosuccinimide provided (XI). The acetamide function of (XI) was then hydrolyzed in refluxing 2M HCl to give amine (XII). Finally, coupling of (XII) with isocyanate (IV) gave rise to the corresponding urea.

参考文献中间体

【1】 Evans, M.; Gaster, L.M.; Gordon, l.; et al.; Mixed 5-HT1A/1B/1D receptor antagonists as novel antidepressants. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PB-77.
【2】 Gaster, L.M.; Rami, H.K.; Wyman, P.A. (SmithKline Beecham plc); Indole derivs. having combined 5HT1A, 5HT1B and 5HT1D receptor antagonist activity. EP 0975593; WO 9850358 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	44709	4-(4-pyridinyl)-1-naphthyl isocyanate; 4-(4-isocyanato-1-naphthyl)pyridine		C₁₆H₁₀N₂O	详情	详情
(V)	44710	1-(6-nitro-2,3-dihydro-1H-indol-1-yl)-1-ethanone		C₁₀H₁₀N₂O₃	详情	详情
(VI)	44711	1-(6-amino-2,3-dihydro-1H-indol-1-yl)-1-ethanone		C₁₀H₁₂N₂O	详情	详情
(VII)	44712	1-(6-bromo-2,3-dihydro-1H-indol-1-yl)-1-ethanone		C₁₀H₁₀BrNO	详情	详情
(VIII)	44713	2-chloro-N-(2-chloroethyl)-N-methyl-1-ethanamine; N,N-bis(2-chloroethyl)-N-methylamine		C₅H₁₁Cl₂N	详情	详情
(IX)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情
(X)	44714	1-[6-(4-methyl-1-piperazinyl)-2,3-dihydro-1H-indol-1-yl]-1-ethanone		C₁₅H₂₁N₃O	详情	详情
(XI)	44715	1-[5-chloro-6-(4-methyl-1-piperazinyl)-2,3-dihydro-1H-indol-1-yl]-1-ethanone		C₁₅H₂₀ClN₃O	详情	详情
(XII)	44716	5-chloro-6-(4-methyl-1-piperazinyl)indoline		C₁₃H₁₈ClN₃	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)