2-[(6aR,9S,10aR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]acetonitrile -Drug Synthesis Database

【结构式】

【分子编号】40431

【品名】2-[(6aR,9S,10aR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]acetonitrile

【CA登记号】

【分子式】C₁₇H₁₉N₃

【分子量】265.35808

【元素组成】C 76.95% H 7.22% N 15.84%

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)

It is prepared in two different ways, both starting from 6-methyl-8-methanesulfonyloxymethylergolin (II), m.p. 192-4 C, prepared by reaction of the corresponding hydroxy compound (I) with methanesulfonyl chloride in pyridine: 1) The starting product (II) is first chlorinated with N-chlorosuccinimide (A) in dioxane to 2-chloro-6-methyl-8-methanesulfonyloxymethylergolin (III), which is then treated with sodium cyanide in DMSO. 2) The starting product (II) is first treated with sodium cyanide in DMSO to give 6-methyl-8-cyanomethylergolin (IV), which is then chlorinated with N-chlorosuccinimide (A) in dioxane.

参考文献中间体

合成目标

【1】 Castañer, J.; Chatterjee, S.S.; Lergotrile. Drugs Fut 1976, 1, 2, 63.
【2】 Clemens, J.A.; et al. (Eli Lilly and Company); D-6-methyl-2,8-disubstituted ergolines. DE 2335750; ES 446789; FR 2193606; GB 1423065; JP 57081487 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	40429	Succinchlorimide; N-Chlorosuccinimide; 1-chloro-2,5-pyrrolidinedione	128-09-6	C₄H₄ClNO₂	详情	详情
(I)	10051	[(6aR,9R,10aR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]methanol; 9,10-Dyhydrosergol	18051-16-6	C₁₆H₂₀N₂O	详情	详情
(II)	40428	(6aR,9R,10aR)-7-methyl-9-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline		C₁₉H₂₆N₂OS	详情	详情
(III)	40430	(6aR,9R,10aR)-5-chloro-7-methyl-9-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline		C₁₉H₂₅ClN₂OS	详情	详情
(IV)	40431	2-[(6aR,9S,10aR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]acetonitrile		C₁₇H₁₉N₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：

Chromanone (II) was prepared by reaction of 2',5'-dihydroxyacetophenone (I) with acetone and pyrrolidine. Alkylation of the hydroxyl group of (II) with 4,4,4-trifluorobutyl bromide in the presence of NaH provided ether (III). The keto group of (III) was then reduced to alcohol (IV), which was subsequently dehydrated to chomene (V) by means of p-toluenesulfonic acid in hot toluene. Asymmetric epoxidation of (V) with NaOCl employing the chiral auxiliary (R,R)-bis(3,5-di-tert-butylsalicylidene)-1,2-diaminocyclohexane manganese (III) chloride furnished epoxide (VI). Finally, epoxide opening by the sodium salt of N-methyl methanesulfonamide afforded the title compound.

参考文献中间体

合成目标

【1】 Lang, H.J.; Gerlach, U.; Weldmann, K.; Brendel, J. (Aventis Pharma Deutschland GmbH); Sulphonamide substd. benzopyran derivs., process of preparation, their use as medicines and pharmaceutical compsns. containing them. CA 2252733; DE 19748469; EP 0913396; JP 1999222485; US 6008245 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40431	2-[(6aR,9S,10aR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]acetonitrile		C₁₇H₁₉N₃	详情	详情
	40730	1-Bromo-4,4,4-trifluorobutane 1-Bromo-4,4,4-trifluorobutane	406-81-5	C₄H₆BrF₃	详情	详情
(I)	38479	1-(2,5-dihydroxyphenyl)-1-ethanone	490-78-8	C₈H₈O₃	详情	详情
(II)	38480	6-hydroxy-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one		C₁₁H₁₂O₃	详情	详情
(III)	38481	2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-2,3-dihydro-4H-chromen-4-one		C₁₅H₁₇F₃O₃	详情	详情
(IV)	38482	2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-4-chromanol		C₁₅H₁₉F₃O₃	详情	详情
(V)	38483	2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-2H-chromene; 2,2-dimethyl-2H-chromen-6-yl 4,4,4-trifluorobutyl ether		C₁₅H₁₇F₃O₂	详情	详情
(VI)	38484	(1aR,7bR)-2,2-dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-6-yl 4,4,4-trifluorobutyl ether; (1aR,7bR)-2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-1a,7b-dihydro-2H-oxireno[2,3-c]chromene		C₁₅H₁₇F₃O₃	详情	详情

Extended Information