67045-01-6

Basic information

• Product Name: N-Benzylmalonamic acid
• Synonyms: N-Benzylmalonamic acid
• CAS NO: 67045-01-6
• Molecular Formula: C₁₀H₁₁NO₃
• Molecular Weight: 193.19924
• Mol File: 67045-01-6.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: N-Benzylmalonamic acid(CAS DataBase Reference)
• NIST Chemistry Reference: N-Benzylmalonamic acid(67045-01-6)
• EPA Substance Registry System: N-Benzylmalonamic acid(67045-01-6)

Safety Data

• Hazardous Substances Data: 67045-01-6(Hazardous Substances Data)

Upstream product

• 29689-63-2 ethyl (N-benzylcarbamoyl)acetate 
• 4279-77-0 S-phenyl hydrogen thiomalonate 
• 100-46-9 benzylamine 
• 36239-09-5 ethyl chlorocarbonylacetate 
• 308821-19-4 malonic acid benzyl ester benzylamide 
• 66825-16-9 methyl 3-oxo-3-[(phenylmethyl)amino]propanoate 
• 2033-24-1 cycl-isopropylidene malonate 

Downstream Products

• 1025894-05-6 PhCH₂NHCO-CH₂-CONH-Trp-(NMe)Nle-Asp(OBzl)-Phe-NH₂ 
• 1391571-92-8 N₁-(2-(1H-indol-3-yl)ethyl)-N₁,N₃-dibenzylmalonamide 
• 66825-16-9 methyl 3-oxo-3-[(phenylmethyl)amino]propanoate 
• 588-46-5 N-(phenylmethyl)acetamide 
• 612095-65-5 (E)-3-(4-methoxyphenyl)-N-phenylmethyl-2-propenamide 

Relevant articles and documents

Knoevenagel condensation of unsymmetrieal malonamic esters and malonates on a solid support

The solid phase synthesis of unsymmetrical substituted methylene malonamic acids 7 and methylene malonic ester mono acids 8 is reported. Resin-bound malonic acid 3 is obtained by treatmeat of Wang's resin with Meldrum's acid. The free carboxylic acid can be derivatized to afford either esters or amides, which readily undergo Knoevenagel condensation with aldehydes. Cleavage with TFA affords unsymmetrical β-substituted methylene malonamic acids or malonate mono acids.

Rapid access to cinnamamides and piper amides: Via three component coupling of arylaldehydes, amines, and Meldrum's acid

A practical method for the synthesis of cinnamamides and piper amides via a conceptually novel three component reaction of aldehydes, amines and Meldrum's acid has been reported. The reaction proceeds under operationally simple conditions without the aid of coupling reagents, oxidants, or catalysts, which are essential for the preparation of cinnamamides/piper amides via known methods. The formation of undesired chemical wastes that generally originate from the use of coupling reagents, oxidants, or catalysts has been avoided to make this reaction more atom economical.

Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox

Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.

Novel malonamide derivatives as potent κ opioid receptor agonists

A novel series of malonamide derivatives was synthesized. These amides were shown to be potent and selective κ opioid receptor agonists.

Amide derivatives and methods of their use

Amide derivatives of the general formulae Ia and Ib: are disclosed. Pharmaceutical compositions containing these compounds, and methods for their use, inter alia, for treating and/or preventing gastrointestinal disorders, pain, and pruritus are also disclosed.

Replacement of glycine with dicarbonyl and related moieties in analogues of the C-terminal pentapeptide of cholecystokinin: CCK2 agonists displaying a novel binding mode

Recent advances in the field of cholecystokinin have indicated the possible occurrence of multiple affinity states of the CCK2 receptor. Besides, numerous pharmacological experiments performed 'in vitro' and 'in vivo' support the eventuality of different pharmacological profiles associated to CCK2 ligands. Indeed, some agonists are essentially anxiogenic and uneffective in memory tests, whereas others are not anxiogenic and appear as able to reinforce memory. The reference compound for the latter profile is the CCK-8 analogue BC 264 (Boc-Tyr(SO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2). However, although tetrapeptide ligands based on CCK-4 (Trp-Met-Asp-Phe-NH2) are known to possess sufficient structural features for CCK2 recognition, none shares the properties of BC 264. Hence we have developed new short peptidic or pseud-opeptidic derivatives containing the C-terminal tetrapeptide of BC 264. Our results indicate that some compounds characterized by the presence of two carbonyl groups at the N-terminus, as in 2b (HO2C-CH2-CONH-Trp-(NMe)Nle-Asp-Phe-NH2), are likely to show a BC 264-like profile, bind to the CCK2 receptor in a specific way, and display remarkable affinities (2b: 0.28 nM on guinea-pig cortex membrane preparations). This original binding mode is discussed and further enlightened by NMR and molecular modeling studies.

Malonylcoenzyme A Models. Part 2. The Methylene Deprotonation Step of the E1cB Acyl Transfer of Malonic Acid Thiolmonoesters

The deprotonation of the α-methylene site in S-aryl hydrogenthiomalonates (HO2CCH2COSR) was general-base catalysed.Nitrogen bases fit a single Broensted correlation for this deprotonation step with slope 0.59 for primary, secondary, and tertiary amines.In general, amines followed saturation kinetics, but hydroxylamine followed the rate law kobs = k1 + k22; nevertheless, the k1 parameter fitted the Broensted correlation for nitrogen bases.Oxygen-based buffers fitted an independent Broensted correlation with β 0.42 and were slightly less reactive than nitrogen bases for a given catalyst pKa.Saturation kinetics were observed for thiolysis of S-4-chlorophenyl hydrogenthiomalonate, implying a ketenoid (E1cB) pathway for the malonyl transfer.The primary isotope effect (H/D) for N-methylmorpholine catalysed deprotonation (dedeuteriation) of HO2C.CH2COSPh and DO2C.CD2COSPh was ca. 3.6.The second-order rate constant for ethylamine attack on S-4-chlorophenyl hydrogen-(2,2-dimethyl)-thiomalonate was 600-fold smaller than that estimated at lower buffer concentrations for S-4-chlorophenyl hydrogenthiomalonate, in accord with general-base catalysed deprotonation mechanism for the latter.The 2,2-dimethylmalonate ester showed a marked rate of attack of water on the monoanion probably reflecting intramolecular general-base catalysis by the -CO2- group.Second-order rate constants for hydroxide ion attack on S-phenyl and S-4-chlorophenyl hydrogenthiomalonates were measured.