Nucleic Acid Related Compounds. 118. Nonaqueous Diazotization of Aminopurine Derivatives. Convenient Access to 6-Halo- and 2,6-Dihalopurine Nucleosides and 2‘-Deoxynucleosides with Acyl or Silyl Halides¹

Abstract

Treatment of 9-(2,3,5-tri-O-acetyl-beta-d-ribofuranosyl)-2-amino-6-chloropurine (1) with TMS-Cl and benzyltriethylammonium nitrite (BTEA-NO2) in dichloromethane gave the crystalline 2,6-dichloropurine nucleoside 2, and acetyl chloride/BTEA-NO2 was equally effective ( approximately 85%, without chromatography). TMS-Br/tert-butyl nitrite/dibromomethane gave crystalline 2-bromo-6-chloro analogue 3 (85%). (Chloro or bromo)-dediazoniation of 3',5'-di-O-acetyl-2'-deoxyadenosine (4) gave the 6-[chloro (5, 63%) or bromo (6, 80%)]purine deoxynucleosides, and 2',3',5'-tri-O-acetyladenosine (8) was converted into the 6-chloropurine nucleoside 9 (71%).

New highly active antiplatelet agents with dual specificity for platelet P2Y1 and P2Y12 adenosine diphosphate receptors

“…2-Bromoadenosine [43], needed for compound 11 , was prepared in 3 steps from guanosine through 2′,3′,5′-tri- O -acetylguanosine, 2-amino-6-chloro-9-(2′,3′,5′-tri- O -acetyl-β-D-ribofuranosyl)purine [46], and 2-bromo-6-chloro-9-(2′,3′,5′-tri- O -acetyl-β-D-ribofuranosyl)purine [47], as described.…”

Investigations into the Origin of the Molecular Recognition of Several Adenosine Deaminase Inhibitors

“…Thus, treatment of 8-aza-2-HexS-adenosine-2 0 ,3 0 ,5 0 -tribenzoate, 42, with a 5-fold excess of AcCl/BTEA-NO 2 in CH 2 Cl 2 at 0-5°C for 4 h, 58 gave the desired product in 60% yield.…”

CC Cross‐Coupling Reactions of O6‐Alkyl‐2‐Haloinosine Derivatives and a One‐Pot Cross‐Coupling/O6‐Deprotection Procedure

“…We chose 2-bromo-2’,3’,5’-tri- O -( t -butyldimethylsilyl)- O 6 -methylinosine ( 1 , a riboside) for our initial studies for the following reasons: ribonucleosides are more economical than their deoxy analogues and O 6 -protection as a methyl ether, by using our reported procedure, [17] is more convenient than the Mitsunobu reaction that would otherwise be required. [16,18,19] Thus, 2’,3’,5’-tri- O -( t -butyldimethylsilyl)- O 6 -methylguanosine was brominated by using t -BuONO/TMSBr (TMS = trimethylsilyl) in CH 2 Br 2 [19,20] to afford the requisite precursor ( 1 ; for details, see the Supporting Information). Pd(OAc) 2 and [Pd 2 (dba) 3 ] were chosen as metal sources in combinations with five ligands ( L1 – L5 ; Scheme 1).…”

“…For this evaluation, 2’,3’,5’-tri- O -( t -butyldimethysilyl)-2-chloro -O 6 -methylinosine ( 3 ) was synthesized by diazotization/chlorination with t BuONO and TMSCl in CH 2 Cl 2 (for details, see the Supporting Information). [20] Then, Chloro-nucleoside 3 was evaluated in C–C cross-coupling reactions under the same conditions as for compound 1 (Table 3). …”