- Synthesis, experimental and computational studies of N-(4-amino-6-oxo-1,6-dihydropyrimidin-5-yl)benzamide
-
Background: Blockade of kainate receptors is an emerging strategy to treat neurodegenera-tive diseases, including Parkinson’s disease as well as to treat epilepsy. In particular, non-competitive antagonists of kainate receptors are promising due to the expected good safety profile. We present here synthesis, experimental and computational studies of N-(4-amino-6-oxo-1,6-dihydropyrimidin-5-yl)benzamide which is an intermediate in the synthesis of hypoxanthine derivatives which were designed as non-competitive antagonists of kainate GluK1/GluK2 receptors. Method: The title compound was obtained in a five-step synthesis protocol and characterized used X-ray crystallography and experimental and computed spectra. Results: The presented detailed X-ray studies of the title compound confirm the reaction course. The title compound crystallizes in triclinic P-1 space group. The asymmetric unit comprises two independent molecules of the compound (A and B) and a DMF solvent molecule. The interpretation of IR spectra was facilitated by Potential Energy Distribution (PED) analysis. The low value of HOMO-LUMO gap indicates that the studied compound is relatively reactive. Conclusion: The title compound is a well-characterized intermediate which will be subjected to cycli-zation to hypoxanthine derivative designed as non-competitive antagonist of kainate GluK1 and GluK2 receptors.
- Kaczor, Agnieszka A.,Bartyzel, Agata,Pitucha, Monika,Wróbel, Tomasz M.,Wo?niak, Sylwia,Matosiuk, Dariusz
-
p. 491 - 502
(2019/05/01)
-
- N-Alkylation of 2,6-dichloropurine hydrochloride with a variety of alcohols over alumina catalyst
-
2,6-Dichloropurine hydrochloride reacts with various types of alcohols using different alumina catalysts and converts into its N-9-alkyl-2-chloro-6- hydroxy-9H-purine products to an extent of 49-74%. The product selectivity depends on the stability of carbocation generated from the alcohol. More stable carbocation formulates both N-7 and N-9-alkyl-2,6-dichloropurine products, whereas the less stable carbocation results in exclusively N-9-alkyl-2-chloro-6- hydroxy-9H-purine. The catalytic activity of alumina prepared using the sol-gel method has larger Brunauer, Emmett, and Teller (BET) surface area and hence shows significantly greater catalytic activity than the commercially available alumina samples. Copyright
- Tumma, Harikrishna,Nagaraju,Reddy, K. Vijayakumar
-
scheme or table
p. 1856 - 1866
(2010/07/02)
-
- New N6-substituted 8-alkyl-2-phenylmethylsulfanyl-adenines. II [1]
-
Title compounds bearing substituents on C(2), C(6) and C(8) were prepared from a newly synthesized pyrimidine derivative 11. The new pyrimidine 11 was generated from compound 2 through two different synthetic schemes. In one pathway, compound 2 was nitrosated, reduced and alkylated to produce compounds 9, 10 and 11 respectively (Scheme). In an alternate route using compound 2 as the starting material, a coupling reaction using the diazonium salt derived from p-methylaniline afforded the azo derivative 7, which was subsequently alkylated and reductively cleaved to form compounds 8 and 11 respectively (See Scheme). Compound 11 was annulated to the corresponding hypoxanthine derivatives 12-14; compounds 12 and 13 were chlorinated with phosphorus oxychloride, then reacted with amines to yield compound 17 and 20 respectively. Compounds 21, 22 and 23 were obtained by oxidation of the corresponding sulfide as depicted in Scheme. Alkylation of the thiol function of 1 gave a mixture of 3 and 4. Compound 3 was chlorinated to 5. Nitration of 5 resulted in electrophilic aromatic substitution of the aryl ring and concomitant oxidation of the sulfide to the sulfoxide, producing 6.
- Biagi, Giuliana,Giorgi, Irene,Livi, Oreste,Pacchini, Federica,Scartoni, Valerio,Salerni, Oreste LeRoy
-
p. 581 - 585
(2007/10/03)
-
- Structure and Reactions of a Thiazolinopyrimidine Carbinolamine (1)
-
Ethyl 4-chloroacetocetate condenses with 4-amino-6-hydroxy-2-pyrimidinethiol to yield ethyl 3-hydroxy-5-oxo-7-aminothiazolinopyrimidin-3-acetate (3), and not ethyl 3-hydroxy-5-amino-7-oxothiazolinopyrimidin-3-acetate, as previously reported.This compound reacts with ammonia to produce ethyl 4-(6'-amino-4'-oxo-2'-pyrimidinethio)-3-aminocrotonate (8), the open chain structure of which accounts for the cyclization of 3 to the poly-cyclic lactam, 6a-hydroxy-5,6,6a,7-tetrahydro-8-thia-1,4-diazabicyclazine-2,5-dione, rather than the sterically more favorable lactone, when 3 was treated with triethylamine.Some other reactions of 3 are described, and the structure of 3 and 8 were confirmed by single crystal X-ray diffraction analysis.
- Campaigne, E.,Folting, K.,Huffman, J. C.,Selby, T. P.
-
p. 575 - 580
(2007/10/02)
-
