3-isocyanatopyridine -Drug Synthesis Database

【结构式】

【分子编号】27045

【品名】3-isocyanatopyridine

【CA登记号】15268-31-2

【分子式】C₆H₄N₂O

【分子量】120.11064

【元素组成】C 60% H 3.36% N 23.32% O 13.32%

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：(II)

The heating of nicotinoyl azide (I) in refluxing toluene gives the corresponding isocyanate (II), which without isolation is condensed with 6-chloro-5-(methylsulfanyl)indoline (IV) to afford the target compound. Intermediate indoline (IV) is obtained by reduction of 6-chloro-5-(methylsulfanyl)indole (III) with NaBH3CN in HOAc.

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 .
【2】 Davies, D.T.; Bromidge, S.M.; Dabbs, S.; et al.; Model studies on a synthetically facile series of N-substituted phenyl-N'-pyridin-3-yl ureas leading to 1-(3-pyridylcarbamoyl)indolines that are potent and selective 5-HT2C/2B receptor antagonists. Bioorg Med Chem 1999, 7, 12, 2767.

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)	13619	Nicotinoyl azide		C₆H₄N₄O	详情	详情
(II)	27045	3-isocyanatopyridine	15268-31-2	C₆H₄N₂O	详情	详情
(III)	43774	6-chloro-5-(methylsulfanyl)-1H-indole; 6-chloro-1H-indol-5-yl methyl sulfide		C₉H₈ClNS	详情	详情
(IV)	43775	6-chloro-5-(methylsulfanyl)indoline; 6-chloro-2,3-dihydro-1H-indol-5-yl methyl sulfide		C₉H₁₀ClNS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The reaction of 6-(trifluoromethyl)indoline (I) with potassium thiocyanate and Br2 in methanol gives 5-thiocyanato-6-(trifluoromethyl)indoline (II), which is treated with ammonia in hot dioxane/water yielding the disulfide (III). The acylation of (III) with acetic anhydride and triethylamine in dichloromethane affords the corresponding diacetyl derivative (IV), which is treated with triphenylphosphine and conc. HCl in refluxing dioxane to give 5-sulfanyl-6-(trifluoromethyl)-indoline (V). The methylation of (V) with methyl iodide and K2CO3 in hot DMF yields the methylsulfanyl compound (VI), which is deacetylated with NaOH in refluxing ethanol/water affording 5-(methylmsulfanyl)-6--(trifluoromethyl)-indoline (VII). Finally, this compound is condensed with 3-pyridyl isothiocyanate (VIII) in toluene. The indoline (VII) can also be obtained directly from indoline (I) by reaction of (I) with potassium thiocyanate and Br2 in methanol, followed by a treatment with methyl iodide and KOH. The 3-pyridyl isocyanate can be obtained by decomposition of pyridine-3-carboxylic acid azide (IX) in refluxing toluene.

参考文献中间体

合成目标

【1】 Bromidge, S.M.; et al.; Novel and selective 5-HT2C/2B receptor antagonists as potential anxiolytic agents: Synthesis, quantitative structure-activity relationships, and molecular modeling of substituted 1-(3-pyridylcarbamoyl)indolines. J Med Chem 1998, 41, 10, 1598.

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)	27038	6-(trifluoromethyl)indoline		C₉H₈F₃N	详情	详情
(II)	27039	6-(trifluoromethyl)-5-indolinesulfenyl cyanide		C₁₀H₇F₃N₂S	详情	详情
(III)	27040	6-(trifluoromethyl)-5-[[6-(trifluoromethyl)-2,3-dihydro-1H-indol-5-yl]disulfanyl]indoline		C₁₈H₁₄F₆N₂S₂	详情	详情
(IV)	27041	1-[5-[[1-acetyl-6-(trifluoromethyl)-2,3-dihydro-1H-indol-5-yl]disulfanyl]-6-(trifluoromethyl)-2,3-dihydro-1H-indol-1-yl]-1-ethanone		C₂₂H₁₈F₆N₂O₂S₂	详情	详情
(V)	27042	1-[5-sulfanyl-6-(trifluoromethyl)-2,3-dihydro-1H-indol-1-yl]-1-ethanone		C₁₁H₁₀F₃NOS	详情	详情
(VI)	27043	1-[5-(methylsulfanyl)-6-(trifluoromethyl)-2,3-dihydro-1H-indol-1-yl]-1-ethanone		C₁₂H₁₂F₃NOS	详情	详情
(VII)	27044	5-(methylsulfanyl)-6-(trifluoromethyl)indoline		C₁₀H₁₀F₃NS	详情	详情
(VIII)	27045	3-isocyanatopyridine	15268-31-2	C₆H₄N₂O	详情	详情
(IX)	13619	Nicotinoyl azide		C₆H₄N₄O	详情	详情

Extended Information