ethyl 2-cyano-2-(4,4-dipropylcyclohexylidene)acetate -Drug Synthesis Database

【结构式】

【分子编号】13412

【品名】ethyl 2-cyano-2-(4,4-dipropylcyclohexylidene)acetate

【CA登记号】

【分子式】C₁₇H₂₇NO₂

【分子量】277.40692

【元素组成】C 73.61% H 9.81% N 5.05% O 11.53%

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 hindered base, diisobutylamine, was used in the Stork enamine synthesis of valeraldehyde (I) with allyl bromide to yield the desired aldehyde (II) following acidic hydrolysis and subsequent hydrogenation. Acid-catalyzed annelation of (II) with methyl vinyl ketone provided 4,4-dipropylcyclohex-2-enone which upon hydrogenation gave (III). Piperidine-catalyzed condensation of ethyl cyanoacetate with (III) gave cyanoester (IV). Michael addition of KCN followed by acidic hydrolysis gave diacid (V). Treatment of diacid (V) with acetic anhydride gave desired anhydride (VI), which was condensed with N,N-dimethylaminopropylamine to yield the desired imide (VII). Lithium aluminum hydride reduction of the imide (VII) gave the desired diamine which was treated with anhydrous HCl/ethanol to give the required dihydrochloride salt, SK&F 105685.

参考文献中间体

合成目标

【1】 Curphey, T.J.; Chu, C.C.C.; Hung, J.C.; A study of the alkylation of enamines derived from sterically hindered amines. J Org Chem 1975, 40, 607-14.
【2】 Flaugh, M.E.; Crowell, T.A.; Farlow, D.S.; Acid-catalyzed annelation of alpha-alkyl aldehydes and alpha,beta-unsaturated ketones. A one-pot synthesis of 4,4-dimethyl-2-cyclohexen-1-one. J Org Chem 1980, 45, 5399-400.
【3】 Schwartz, D.A.; Badger, A.M.; SK&F-105685. Drugs Fut 1991, 16, 9, 815.

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)	13409	n-Valeraldehyde; Pentanal	110-62-3	C₅H₁₀O	详情	详情
(II)	13410	2-Propylpentanal		C₈H₁₆O	详情	详情
(III)	13411	4,4-Dipropylcyclohexanone	123018-62-2	C₁₂H₂₂O	详情	详情
(IV)	13412	ethyl 2-cyano-2-(4,4-dipropylcyclohexylidene)acetate		C₁₇H₂₇NO₂	详情	详情
(V)	13413	1-(Carboxymethyl)-4,4-dipropylcyclohexanecarboxylic acid		C₁₅H₂₆O₄	详情	详情
(VI)	13414	8,8-Dipropyl-2-oxaspiro[4.5]decane-1,3-dione		C₁₅H₂₄O₃	详情	详情
(VII)	13415	2-[3-Ddimethylamino)propyl]-8,8-dipropyl-2-azaspiro[4.5]decane-1,3-dione		C₂₀H₃₆N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Piperidine-catalyzed condensation of ethyl cyanoacetate with (I) (1) afforded cyanoester (II). Michael addition of KCN to (II) gave dinitrile (III), which was hydrolyzed under basic conditions to afford diacid (IV). Condensation of (IV) with N,N-diethylaminopropylamine afforded the desired imide (V). Reduction of (V) with lithium aluminum hydride gave the required diamine which was treated with aqueous HCl/n-propanol to yield the diamine as the dihydrochloride salt, SK&F 106615-A2 (VI).

参考文献中间体

合成目标

【1】 Wright, C.S.; Bagder, A.; SK&F-106615. Drugs Fut 1995, 20, 9, 893.
【2】 Badger, A.M.; Dimartino, M.J.; Mirabelli, C.K.; Cheeseman, E.N.; Dorman, J.W.; Picker, D.H.; Schwartz, D.A. (SmithKline Beecham plc); Immunomodulatory azaspiranes. AU 8825333; EP 0310321; JP 1991500290; US 4963557; WO 8902889 .

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)	13411	4,4-Dipropylcyclohexanone	123018-62-2	C₁₂H₂₂O	详情	详情
(II)	13412	ethyl 2-cyano-2-(4,4-dipropylcyclohexylidene)acetate		C₁₇H₂₇NO₂	详情	详情
(III)	16471	1-(cyanomethyl)-4,4-dipropylcyclohexanecarbonitrile		C₁₅H₂₄N₂	详情	详情
(IV)	13413	1-(Carboxymethyl)-4,4-dipropylcyclohexanecarboxylic acid		C₁₅H₂₆O₄	详情	详情
(V)	16473	2-[3-(diethylamino)propyl]-8,8-dipropyl-2-azaspiro[4.5]decane-1,3-dione		C₂₂H₄₀N₂O₂	详情	详情

Extended Information