32118-53-9

Usage

Synthesis Reference(s)

Journal of the American Chemical Society, 78, p. 5416, 1956 DOI: 10.1021/ja01601a068

InChI:InChI=1/C8H16O2/c1-5(2)7(6(3)4)8(9)10/h5-7H,1-4H3,(H,9,10)

Upstream product

• 5440-65-3 diisopropylethyl amide 
• 94991-59-0 methyl 2-isopropyl-3-methylbutanoate 
• 866-29-5 2-cyano-2-isopropyl-3-methyl-butyric acid 
• 1735-09-7 diisopropyl-malonic acid 
• 75-30-9 2-iodo-propane 
• 503-74-2 3-methylbutyric acid 
• 7498-49-9 diisopropyl-malonic acid monomethyl ester 
• 1888-57-9 2,5-dimethylhexan-3-one 
• 62391-96-2 3-Methyl-2-isopropylbutyronitrile 
• 99176-61-1 2,2-diisopropyl-malonamic acid methyl ester 
• 7499-15-2 2,2-Diisopropylmalonsaeuremonoamid 
• 66730-62-9 C₅H₈O₂^(2-)*2Li⁽¹⁺⁾ 
• 7647-01-0 hydrogenchloride 

Downstream Products

• 94991-59-0 methyl 2-isopropyl-3-methylbutanoate 

Relevant academic research and scientific papers

Syntheses and evaluation of anticonvulsant activity of novel branched alkyl carbamates

A novel class of 19 carbamates was synthesized, and their anticonvulsant activity was comparatively evaluated in the rat maximal electroshock (MES) and subcutaneous metrazol (scMet) seizure tests and pilocarpine-induced status epilepticus (SE) model. In spite of the alkyl-carbamates' close structural features, only compounds 34, 38, and 40 were active at the MES test. The analogues 2-ethyl-3-methyl-butyl-carbamate (34) and 2-ethyl-3-methyl-pentyl- carbamate (38) also exhibited potent activity in the pilocarpine-SE model 30 min postseizure onset. Extending the aliphatic side chains of homologous carbamates from 7 to 8 (34 to 35) and from 8 to 9 carbons in the homologues 38 and 43 decreased the activity in the pilocarpine-SE model from ED50 = 81 mg/kg (34) to 94 mg/kg (35) and from 96 mg/kg (38) to 114 mg/kg (43), respectively. The most potent carbamate, phenyl-ethyl-carbamate (47) (MES ED50 = 16 mg/kg) contains an aromatic moiety in its structure. Compounds 34, 38, 40, and 47 offer the optimal efficacy-safety profile and, consequently, are promising candidates for development as new antiepileptics.

Syntheses and evaluation of anticonvulsant profile and teratogenicity of novel amide derivatives of branched aliphatic carboxylic acids with 4-aminobenzensulfonamide

Despite the availability of 14 new antiepileptic drugs (AEDs), about 30% of epileptic patients are not seizure-free. Consequently there is substantial need to develop new effective AEDs. A novel class of aromatic amides composed of phenylacetic acid or branched aliphatic carboxylic acids, with five to nine carbons in their carboxylic moiety, and aminobenzenesulfonamide were synthesized and evaluated in the anticonvulsant rat-maximal electroshock (MES) and subcutaneous metrazol seizure (scMet) tests. Fourteen of the synthesized amides had an anticonvulsant ED50 of 50 values of 7.6, 9.9, and 9.4 mg/kg and remarkable protective index (PI = TD 50/ED50) values of 65.7, 50.5, and 53.2, respectively. These potent sulfanylamides caused neural tube defects only at doses markedly exceeding their effective dose. The anticonvulsant properties of these compounds make them potential candidates for further development as new, potent, and safe AEDs.

Synthesis and evaluation of antiallodynic and anticonvulsant activity of novel amide and urea derivatives of valproic acid analogues

Valproic acid (VPA, 1) is a major broad spectrum antiepileptic and central nervous system drug widely used to treat epilepsy, bipolar disorder, and migraine. VPA's clinical use is limited by two severe and lifethreatening side effects, teratogenicity and hepatotoxicity. A number of VPA analogues and their amide, N-methylamide and urea derivatives, were synthesized and evaluated in animal models of neuropathic pain and epilepsy. Among these, two amide and two urea derivatives of 1 showed the highest potency as antineuropathic pain compounds, with ED50 values of 49 and 51 mg/kg for the amides (19 and 20) and 49 and 74 mg/kg for the urea derivatives (29 and 33), respectively. 19, 20, and 29 were equipotent to gabapentin, a leading drug for the treatment of neuropathic pain. These data indicate strong potential for the above-mentioned novel compounds as candidates for future drug development for the treatment of neuropathic pain. 2009 American Chemical Society.

Potent anticonvulsant urea derivatives of constitutional isomers of valproic acid

Valproic acid (VPA) is a major antiepileptic drug (AED); however, its use is limited by two life-threatening side effects: teratogenicity and hepatotoxicity. Several constitutional isomers of VPA and their amide and urea derivatives were synthesized and evaluated in three different anticonvulsant animal models and a mouse model for AED-induced teratogenicity. The urea derivatives of three VPA constitutional isomers propylisopropylacetylurea, diisopropylacetylurea, and 2-ethyl-3-methyl-pentanoylurea displayed a broad spectrum of anticonvulsant activity in rats with a clear superiority over their corresponding amides and acids. Enanatiomers of propylisopropylacetylurea and propylisopropylacetamide revealed enantioselective anticonvulsant activity, whereas only enantiomers of propylisopropylacetylurea displayed enantioselective teratogenicity. These potent urea derivatives caused neural tube defects, but only at doses markedly exceeding their effective dose, whereas VPA showed no separation between its anticonvulsant activity and teratogenicity. The broad spectrum of anticonvulsant activity of the urea derivatives coupled with their wide safety margin make them potential candidates to become new, potent AEDs.

Analogs of isovaleramide, a pharmaceutical composition including the same, and a method of treating central nervous system conditions or diseases

An isovaleramide analog having at least one of an increased potency, an increased half-life, and an increased stability compared to isovaleramide. The isovaleramide analog is a cyclic analog or a noncyclic analog. The isovaleramide analog is formulated into a pharmaceutical composition. A method of treating a central nervous system condition or disease is also disclosed. The method comprises administering an isovaleramide analog to a patient suffering from the central nervous system condition or disease.

HETEROCUMULENES IN ACYLATION REACTIONS II. REACTIVITY OF ALKYL-SUBSTITUTED KETENES IN SPONTANEOUS HYDROLYSIS REACTIONS

The structures and electronic states of six ketenes were investigated by the semiempirical MNDO, MINDO/3, and AM1 quantum-chemical methods.The kinetics of the spontaneous hydrolysis of mono- and dialkylsubstituted ketenes in water and water-acetonitrile mixtures at 20 deg C were studied.The induction and steric effects of the substituents on the process rate were evaluated quantitatively in terms of a ρ? analysis.An increase in the number, length, and branching of the hydrocarbon substituents at the terminal carbon atom of the ketenes leads to a large decrease in the hydrolysis rate.The results of the calculations were compared with experimental data.Possible alternatives for the mechanism of the process are discussed.

C-C Cleavage of Ionized Carboxylic Acids as Reversal of Additions of Alkyl Radicals to Protonated α,β-Unsaturated Acids. - On the Role of Enol Cation Radicals as Reactive Intermediates in Isomerization/Dissociation Reactions in the Gas Phase

Metastable molecular ions of pivalic acid (5) and 2-methylbutanoic acid (8) decompose unimolecularly via methyl loss, thereby specifically generating protonated crotonic acid (5 -> 6) and protonated methacrylic acid (8 -> 7), respectively.The investigation of 13C and 2H labelled isotopomers of 5 and 8 together with MNDO calculations of parts of the potential energy surface of 8 reveals that C-C cleavage requires the presence of enol cation radicals of the general structure 1 as reactive intermediates.Cation radicals of carboxylic acids in which the radical centre is not adjacent to the protonated carboxylic function, as for example in 3, do not serve as actual precursors for the C-C cleavage; instead, isomerization to 1 is required.The fact that enol cation radicals, i.e. 1, 13 and 14, are of essential importance in the splitting of C-C bonds of ionized carboxylic acids is a direct consequence of the fact that these dissociations can be viewed as the reversal of addition of (nucleophilic) alkyl radicals to protonated α,β-unsaturated acids, which proceeds preferentially via enol cation radical intermediates.

Elargissement du Domaine Structural Ordonne de Reaction (DSOR) dans la synthese de cetones: acces a la serie iPr3CCOR' (3330) (ijkl)

The general pathway for the synthesis of aliphatic ketones limited to the γ position is extended.By two methods, Grignard reaction on acid chlorides (D3Ai) and alkylation (B1), new hindered ketones iPr3CCOR' are obtained.Among these, iPr3CCOCEt2tBu is the most crowded compound obtained.

STERIC EFFECTS IN SYSNTHESIS - STERIC LIMITS TO THE ALKYLATION OF NITRILES AND CARBOXYLIC ACIDS

The steric limits to the alkylation of aliphatic nitriles and carboxylic acids have been investigated in some detail.For the experimental conditions considered (ionization by i-Pr2NLi in THF followed by alkylation with RI/THF/HMPA) the most hindered nitriles R-CN and carboxylic acids R-CO2H have the same secondary alkyl group R=t-BuiPrCH-, but different tertiary, i.e.R=t-BuiPrEtC- or i-Pr3C- for RCN and R=Et2MeC for RCO2H.A comparison of the relative merits of alkylation of esters, carboxylic acids, and nitriles is considered.