- Synthesis process of gabapentin intermediate
-
The invention relates to a synthesis process of a gabapentin intermediate. The intermediate is 1, 1-cyclohexyldiacetic acid. the synthesis process comprises the following steps: cyclizing cyclohexanone and ethyl cyanoacetate to prepare alpha, alpha'-dicyano-1, 1-cyclohexyldiacetylimine ammonium salt, and then hydrolyzing under the action of solid acid to prepare a target product intermediate. The solid acid is prepared by taking montmorillonite intercalated with modified cellulose as a carrier, loading tin ions through an ion exchange method and then carbonizing at low temperature. The synthesis of the gabapentin intermediate is realized by utilizing the self-made solid acid catalyst, the green and environment-friendly concept is compounded, and meanwhile, the yield is relatively high; each preparation process of the catalyst is relatively simple, complicated post-treatment is not needed, the catalyst can be recycled, and the repeated utilization rate is high; and the corrosion of concentrated sulfuric acid to industrial equipment and the pollution to the environment in the traditional process are avoided, and the treatment cost of waste liquid in the later period is reduced.
- -
-
Paragraph 0006; 0036
(2021/12/07)
-
- Impurity of gabapentin and preparation method thereof
-
The invention provides a new unknown impurity compound (VII) for gabapentin and a preparation method thereof, wherein the chemical name is 2 - [1 - [(1, 3 - diaza -2 - aza-spiro [4.5] dec -2 -yl) methyl] cyclohexyl] - acetic acid. The impurities are prepared by reacting (1 -) cyclohexanecarboxylic acid (VI) with gabapentin (I), and the synthetic route is as shown below. The impurities thus obtained can be used to support the quality studies of the impurities and to support the process improvement of gabapentin with regard to the control of the impurities.
- -
-
Paragraph 0029; 0046; 0049; 0050; 0053
(2021/11/27)
-
- Antiarthritic and suppressor cell inducing activity of azaspiranes: Structure-function relationships of a novel class of immunomodulatory agents
-
Spirogermanium (1;8,8-diethyl-N,N-dimethyl-2-aza-8-germaspiro[4.5]decane-2-propanamin e dihydrochloride) is a potent cytotoxic agent in vitro which has demonstrated limited activity in experimental animal tumor models. Subsequently, it has been reported that spirogermanium has antiarthritic and suppressor cell-inducing activity. We have synthesized a series of substituted 8-hetero-2-azaspiro[4.5]decane and 9-hetero-3-azaspiro[5.5]undecane analogues of spirogermanium to identify the heteroatom requirements for in vivo antiarthritic and suppressor cell-inducing activity. This structure-activity relationship study has identified that appropriately substituted silicon and carbon analogues of spirogermanium retain both antiarthritic and immunosuppressive activity, with the 8,8-dipropyl (carbon) analogue being among the most active. Following the identification of N,N-dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2-propanamine dihydrochloride (9) as more active analogue than spirogermanium, a series of 8,8-dipropyl analogues with various amine substituents were synthesized. A number of these analogues had activity similar to that of 9. A correlation between activity in the adjuvant arthritic rat and the ability to induce suppressor cells (r = 0.894, p0.001) suggests an association between the two pharmacologic effects. While the precise biochemical mechanism(s) for the pharmacological activity is unclear, these data suggest that compounds within this series, e.g., N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine dihydrochloride, may provide effective therapy in diseases of autoimmune origin and/or the prevention of rejection in tissue transplantation.
- Badger,Schwartz,Picker,Dorman,Bradley,Cheeseman,DiMartino,Hanna,Mirabelli
-
p. 2963 - 2970
(2007/10/02)
-
- Superoxide Anion Radical (O2-anionradical) Mediated Base Catalyzed Autooxidation of α-Keto Enols
-
Eight 4,4-disubstituted 2-hydroxycyclohexa-2,5-dien-1-ones were prepared by the base-catalysed autooxidation (BCA) of the corresponding 4,4- or 5,5-disubstituted cyclohex-2-en-1-ones.Upon reaction with superoxide anion radical (O2-anionradical, generated from KO2/18-crown-6) in inert nonpolar aprotic media at room temperature, α-keto enols 3a-g undergo initial deprotonation of the enol hydrogen followed by BCA at C3 of the resulting enolate.Aqueous acid workup of the reaction mixture yields lactols 4, while methyl iodide quenching generates methoxy lactones 5.Lactols 4 can be readily converted to their acetoxy analogues 8, opened to aldehydo methyl esters 6, or reduced to the related lactones 7.The latter suggests a convenient one-pot synthesis of 2,3-unsaturated δ-valerolactones from the corresponding cyclohex-2-en-1-ones. 4,4-Diphenyl enol 3h, by contrast, resists BCA (whether mediated by O2-anionradical or t-C4H9O-anion) to the corresponding lactol yielding instead a variety of oxidative cleavage products 13-18. 2-Hydroxyspirodec-1-en-3-one (21) also underwent O2-anionradical-mediated BCA, yielding diacids 22 and 26 as well as lactol 30.The synthetic applications of these results are also discussed.
- Frimer, Aryeh A.,Gilinsky-Sharon, Pessia,Aljadeff, Gladis,Marks, Vered,Rosental, Zilpa
-
p. 4866 - 4872
(2007/10/02)
-
