95087-07-3Relevant academic research and scientific papers
Solvent-Controlled, Site-Selective N-Alkylation Reactions of Azolo-Fused Ring Heterocycles at N1-, N2-, and N3-Positions, Including Pyrazolo[3,4- d]pyrimidines, Purines, [1,2,3]Triazolo[4,5]pyridines, and Related Deaza-Compounds
Bookser, Brett C.,Weinhouse, Michael I.,Burns, Aaron C.,Valiere, Andrew N.,Valdez, Lino J.,Stanczak, Pawel,Na, Jim,Rheingold, Arnold L.,Moore, Curtis E.,Dyck, Brian
, p. 6334 - 6353 (2018/06/01)
Alkylation of 4-methoxy-1H-pyrazolo[3,4-d]pyrimidine (1b) with iodomethane in THF using NaHMDS as base selectively provided N2-methyl product 4-methoxy-2-methyl-2H-pyrazolo[3,4-d]pyrimidine (3b) in an 8/1 ratio over N1-methyl product (2b). Interestingly, conducting the reaction in DMSO reversed selectivity to provide a 4/1 ratio of N1/N2 methylated products. Crystal structures of product 3b with N1 and N7 coordinated to sodium indicated a potential role for the latter reinforcing the N2-selectivity. Limits of selectivity were tested with 26 heterocycles which revealed that N7 was a controlling element directing alkylations to favor N2 for pyrazolo- and N3 for imidazo- and triazolo-fused ring heterocycles when conducted in THF. Use of 1H-detected pulsed field gradient-stimulated echo (PFG-STE) NMR defined the molecular weights of ionic reactive complexes. This data and DFT charge distribution calculations suggest close ion pairs (CIPs) or tight ion pairs (TIPs) control alkylation selectivity in THF and solvent-separated ion pairs (SIPs) are the reactive species in DMSO.
Synthesis of 7-alkynylated 8-aza-7-deaza-2′-deoxyadenosines via the Pd-catalysed cross-coupling reaction
Seela, Frank,Zulauf, Matthias
, p. 3233 - 3239 (2007/10/03)
The synthesis of 7-alkynylated 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidine) 2′-deoxyribonucleosides is described. Nucleobase anion-glycosylation of 8-aza-7-deaza-7-iodo-6-methoxypurine (15) with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride (16) furnishes the 8-aza-7-deaza-7-iodo-6-methoxypurine N1-β-D-2′-deoxyribonucleoside 17a as the main product (38% yield). After detoluoylation of products 17a and 17b27 (→ 19a,b) and amination the 7-bromo and the 7-iodo derivatives of 8-aza-7-deaza-2′-deoxyadenosine (compounds 2b,c) were obtained. Compound 2b served as the starting material for a series of 7-alkynyl- or 7-alkenyl-8-aza-7-deazaadenine 2′-deoxynucleosides 3-13 by employing the Pd0/CuI-catalysed cross-coupling reaction. The 7-halogenated or 7-alkynylated nucleosides show a more stable glycosylic bond than does 8-aza-7-deaza-2′-deoxyadenosine (2a).
Unexpected dehalogenation of 3-bromopyrazolo[3,4-d]pyrimidine nucleosides during nucleobase-anion glycosylation
Seela, Frank,Zulauf, Matthias,Becher, Georg
, p. 305 - 314 (2007/10/03)
The anion-glycosylation (KOH, MeCN, TDA-1) of 3-bromopyrazolo[3,4-d]- pyrimidines 4a and 4b with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro- pentofuranosyl chloride (5) furnishes the regioisomeric N1-β-D-2'- deoxyribonucleosides 6a and 6b together with the dehalogenated N2- regioisomers 8a and 8b, stereoselectively. The dehalogenation takes place after the glycosylation and results from the sensitivity of the N-2 nucleosides toward aqueous base. An addition/elimination mechanism is suggested for the dehalogenation reaction.
