6-chloro-5-methylindoline -Drug Synthesis Database

【结构式】

【分子编号】26798

【品名】6-chloro-5-methylindoline

【CA登记号】

【分子式】C₉H₁₀ClN

【分子量】167.63784

【元素组成】C 64.48% H 6.01% Cl 21.15% N 8.36%

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：(VI)

Alkylation of 3-chloro-4-methylaniline (I) with bromoacetaldehyde diethyl acetal (II) afforded secondary amine (III). Subsequent cyclization of (III) in boiling trifluoroacetic acid/trifluoroacetic anhydride provided a (3:2) mixture of indoles (IV) and (V), from which the desired 6-chloro isomer (IV) was isolated by column chromatography, and then reduced to indoline (VI) using NaBH3CN in AcOH. 5-Aminoquinoline (VII) was treated with carbonyl diimidazole to give intermediate (VIII). This was finally coupled with indoline (VI) in DMF at 100 C to yield the corresponding urea.

参考文献中间体

合成目标

【1】 Ham, P.; Jones, G.E.; Forbes, I.T. (SmithKline Beecham plc); Indoline derivs. as 5HT2C antagonists. EP 0707581; JP 1996512299; US 5834494; WO 9501976 .

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)	26794	3-Chloro-4-methylaniline; 4-Amino-2-chlorotoluene	95-74-9	C₇H₈ClN	详情	详情
(II)	12113	2-Bromo-1-ethoxyethyl ethyl ether; 2-Bromo-1,1-diethoxyethane; Bromoacetaldehyde diethylacetal	2032-35-1	C₆H₁₃BrO₂	详情	详情
(III)	26795	3-chloro-N-(2,2-diethoxyethyl)-4-methylaniline		C₁₃H₂₀ClNO₂	详情	详情
(IV)	26796	6-chloro-5-methyl-1H-indole		C₉H₈ClN	详情	详情
(V)	26797	4-chloro-5-methyl-1H-indole		C₉H₈ClN	详情	详情
(VI)	26798	6-chloro-5-methylindoline		C₉H₁₀ClN	详情	详情
(VII)	26799	5-Aminoquinoline; 5-quinolinamine	611-34-7	C₉H₈N₂	详情	详情
(VIII)	26800	N-(5-quinolinyl)-1H-imidazole-1-carboxamide		C₁₃H₁₀N₄O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Condensation between 3-amino-6-chloropyridazine (I) and 3-hydroxy-2-methylpyridine (II) in aqueous NaOH at 175 C under pressure afforded the bisaryl ether (III). The phenyl carbamate (IV) was then prepared by treatment of aminopyridazine (III) with phenyl chloroformate. Finally, coupling of carbamate (IV) with 6-chloro-5-methylindoline (V) yielded the title urea derivative.

参考文献中间体

合成目标

【1】 Bromidge, S.M.; Davies, S.; Dabbs, S.; et al.; 1-[2-(Heteroaryloxy)heteroaryl]carbamoy]indolines: Novel and selective 5-HT2C receptor inverse agonists with potential as antidepressant/anxiolytic agents. Bioorg Med Chem Lett 2000, 10, 16, 1863.

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)	43962	6-chloro-3-pyridazinamine; 6-chloro-3-pyridazinylamine	5469-69-2	C₄H₄ClN₃	详情	详情
(II)	29609	2-methyl-3-pyridinol	1121-25-1	C₆H₇NO	详情	详情
(III)	43963	6-[(2-methyl-3-pyridinyl)oxy]-3-pyridazinamine; 6-[(2-methyl-3-pyridinyl)oxy]-3-pyridazinylamine		C₁₀H₁₀N₄O	详情	详情
(IV)	43964	phenyl 6-[(2-methyl-3-pyridinyl)oxy]-3-pyridazinylcarbamate		C₁₇H₁₄N₄O₃	详情	详情
(V)	26798	6-chloro-5-methylindoline		C₉H₁₀ClN	详情	详情

Extended Information