152120-56-4

Upstream product

• 62-53-3 aniline 
• 152120-54-2 N,N'-bis( tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidine 
• 322474-21-5 N,N'-bis-Boc-S-methyl-isothiourea 
• 187022-33-9 4-nitro-1-H-pyrazole-1-carboxamidine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 107819-90-9 1,3-bis(tert-butoxycarbonyl)-2-methyl-2-thiopseudourea 
• 145013-05-4 tert-butyl N-({[(tert-butoxy)carbonyl]amino}methanethioyl)carbamate 
• 152120-61-1 tert-butyl (1H-pyrazol-1-ylcarbonoimidoyl)carbamate 
• 332882-82-3 1,3-bis(t-butoxycarbonyl)guanidine 

Downstream Products

• 2002-16-6 1-phenylguanidine 
• 6522-91-4 N-phenyl-guanidine hydrochloride 

Relevant academic research and scientific papers

A convenient and versatile method for the synthesis of protected guanidines

Aromatic, aliphatic and sterically hindered amines react smoothly with commercially available N, N'-bis-BOC-S-methylisothiourea 2 in the presence of mercury chloride to give the protected guanidine in good yield. It is particularly noteworthy that 2 can a

Preparation and evaluation of a polymer-supported Mukaiyama reagent

The synthesis of a polymer-supported Mukaiyama reagent is described. This preparation was thoroughly optimized using a DoE approach to achieve optimum loading, and the procedure was successfully applied to prepare the supported reagent on a 10g scale. This reagent proved to be effective for the formation of carbodiimides through the dehydration of thioureas and for a one-pot guanylation of primary amines.

The utilization of ball milling in synthesis of aryl guanidines through guanidinylation and N-Boc-deprotection sequence

Solid state ball milling was used in guanidinylation reactions of aromatic amines with N,N′-Di-Boc-1H-pyrazole-1-carboxamidine reagent. Reaction conditions are advantageous, and in general reactions proceed in significantly shorter reaction times and in higher yields than under the conventional solution conditions. Mechanochemical conditions were also successfully applied to the cleavage of N-Boc protecting group.

Synthesis of 2-arylamino-5-formyl-pyrimidines from the bis(hexafluorophosphate) Arnold salt

A three-step synthesis of 2-arylamino-5-formyl-pyrimidines is developed by condensation of the bis(hexafluorophosphate) Arnold salt with N-arylguanidines. This method conveniently provides the corresponding 2-arylaminopyrimidine derivatives in good yields

Synthesis of guanidines via the I2 mediated desulfurization of N,N′-di-Boc-thiourea

The I2 mediated desulfurization of N,N′-di-Boc-thiourea was developed. Various primary amines, including sterically and electronically deactivated primary amines, were transformed into the corresponding bis-Boc protected guanidines under mild conditions.

Iodine-catalyzed guanylation of amines with N, N ′-di-Boc-thiourea

Herein, we report that iodine-catalyzed guanylation of primary amines can be accomplished with N,N′-di-Boc-thiourea and TBHP to afford the corresponding guanidines in 40-99% yields. Oxidation of the HI byproduct by TBHP eliminates the need for an extra base to prevent the protonation of substrates and makes the reaction especially useful for both electronically and sterically deactivated primary anilines.

Method for synthesizing substituted guanidine

The invention provides a method for synthesizing substituted guanidine. The method of the invention is provided against heavy metals or complex oxidants needed in convectional methods for synthesizingthe substituted guanidine. The method comprises the following steps: carrying out an elemental iodine-mediated thiourea desulphurization reaction on economical and easily available N,N'-bis-tert-butoxycarbonylthiourea to generate an active carbodiimide active intermediate, and attacking the intermediate with free amine to remove a protecting group in order to finally realize the preparation of the guanidine containing different substituent groups. The method for synthesizing substituted guanidine of the present invention has the advantages of mild reaction conditions and high efficiency, andis expected to be applied to later modification of drug molecules and natural products.

Substituent effects on the basicity (p: K a) of aryl guanidines and 2-(arylimino)imidazolidines: Correlations of pH-metric and UV-metric values with predictions from gas-phase ab initio bond lengths

The dissociation constants of two related series of 2-(arylimino)imidazolidine and aryl guanidine α2-adrenoceptor antagonists (35 compounds in total) were measured by potentiometric titrations and by UV-spectrophotometry using the 96-well microtitre plate method. The experimental values obtained using both methods were quite consistent and showed a very good agreement with the pKa values calculated using the AIBLHiCoS methodology, which uses only a single bond length obtained using ab initio calculations at a low level of theory. The prediction power of the imidazolidine and guanidine set of compounds was very good with deviations typically a units, and a mean absolute error (MAE) of 0.23 and 0.29, respectively. The study of the quantitative effect of diverse substituents on the basicity of aryl guanidine and 2-(arylimino)imidazolidine derivatives is useful for medicinal chemists working with biologically relevant guanidine-containing molecules.

Copper(II) chloride promoted transformation of amines into guanidines and asymmetrical N,N'-disubstituted guanidines

We present a concise, less-toxic and broadly applicable method for coupling weakly nucleophilic amines with N,N'-di-(tert-butoxycarbonyl)thiourea, N-(tert-butxoycarbonyl), N'-alkyl/arylsubstituted-thioureas and N,N'-di-(tert-butoxycarbonyl)imidazolidine-2-thione in the presence of copper(II) chloride. Subsequent removal of Boc protecting groups affords guanidines, di-substituted guanidines and 2-aminoimidazolines in modest to excellent overall yields.

GUANIDINE BASED COMPOUNDS

The adrenergic receptors or adrenoceptors are a family of G-protein coupled receptors split into α and β subclasses. The adrenoceptors have important roles in regulating a myriad of physiological conditions and their malfunction has been implicated in the pathophysiology of a number of diseases. Disclosed herein are a series of novel guanidine and 2-aminoimidazoline compounds which are ligands of the alpha2-adrenoceptor (α2-ARs) subclass of adrenergic receptors. The invention also provides for pharmaceutical compositions comprising the novel compounds. The compounds are suitable for use in the manufacture of medicaments for the treatment of α2-ARs associated disorders, such as depression, schizophrenia, glaucoma and analgesia.