9-Benzyl-6-chloropurine

The Suzuld-Miyaura cross-coupling reaction of 9-benzyl-6-chloropurine with boronic acids gives 6-alkylated purines in moderate to excellent yields. The reaction has been successfully... 

Table 1 Reaction of 9-Benzyl-6-chloropurine (la) with RB(OH)2 (1.2 equiv)...

Many 6-alkylaminopurine nucleosides are important adenosine receptor antagonists, and acyclic nucleotide analogues derived from 6-dialkylaminopurines are strong antivirals, anti-neoplastic agents, and immunomodulators. Recently, several 6-(arylalkynyl)-, 6-(arylalkenyl)-, and 6-(arylalkyl)purines have been reported to exhibit cytokinine activity. Suzuki crosscoupling reactions of 9-benzyl-6-chloropurine with boronic acids have recently been reported to provide 6-substituted purines in moderate to excellent yields (Eq. (46)) [77]. 

Stille coupling between suitable 6-chloropurines and aryl(tributyl)tin afforded 6-arylpurines with a variety of substituents in the 9-position which were screened for antimycobacterial activity <02JMCI383>. The Stille cross-coupling reactions of 1,4- and l,3-bis(trialkylstannyl)benzenes with 9-benzyl-6-chloropurine gave 1,4- and l,3-bis(purin-6-yl)benzenes and 4-(purin-9-yl)benzenes <02T7431>. 

Benzyl-6-chloropurine (5 g, 20.4 mmol) was added in portions over 20 min to stirred, ice cold, 55% aq HI (25 mL). The bright yellow slurry was stirred for an additional 90 min, and the temperature was kept below — 5 C. The slurry was filtered, washed with a little cold water, and then washed with acetone. The air-dried solid residue was suspended in ll O (50 mL) and cooled to 10 "C, and the pH was adjusted to 8.1. Filtration and drying gave a yellow powder yield 6.19 g (90%). Recrystallization (toluene/acetone) gave the analytical sample mp 152-154 °C. 

Amino-9-benzyl-6-chloropurine reacts with 1,4-diazabicyclo[2,2,2]octane (DABCO) in DMF at ambient temperature to yield the salt (102). This reacts with hydroxide ion (pHl 1), also at ambient temperature, to yield the guanine. Refluxing (102) with alcohols in the presence of potassium carbonate yields the 6-alkoxy-9-substituted guanines in yields up to 72% [94JCS(CC)913]. The 6-aza analogue (103) has been obtained from... 

Recently, dipole moments for simple derivatives of the four tautomers of purine have been measured.93,101 Three series of derivatives have been investigated the iV-methyl-8-phenylpurines, the iV-methyl-6-thiomethylpurines, and the N-methyl-6-thiomethyl-8-phenylpurines. The results are summarized in Table VI. It can be seen that these measurements confirm the theoretical predictions very satisfactorily. It must, however, be mentioned that Dyer et al.l0z did not find any appreciable difference in the dipole moments of the 9-benzyl and 7-benzyl derivatives of 6-chloropurine (4.91 and 5.03 D, respectively). Moreover, Weiler-Feilchenfeld and Neiman101... 

Both the CNDO and PPPCI procedures predict that the dipole moments of Iff and IH tautomers should be higher (order of 5-7 D) than the tautomers 9ff and 3ff (about 3-4 D), and measurements of three series of derivatives of the four purine protomers, namely 9-methyl-8-phenyl-, iV-methyl-6-thiomethyl- and A-methyl-6-thiomethyl-8-phenyl-pur-ines, satisfactorily confirm the theoretical predictions (68CR(C)(267)1461, B-70MI40902). However, such differences have not always been noted as with the dipole moments of 9-benzyl- and 7-benzyl-6-chloropurines (69JOC973). The differences in the values and also the direction of the dipole moments (Figure 4) of the purine protomers reflects their different charge distributions (71AHC(13)77). 

The general preparative route to 6-(benzyloxy)purine (4), an analog of the active synthetic cytokinin-6-(benzylamino)purine, involves the reaction of 6-chloropurine with sodium benzox-ide in benzyl alcohol. ... 

Li et al. have also reported the synthesis of 306 from 2-amino-6-chloropurine 313 and 2,3,5-tris-(9-benzyl-[3-D-arabinofuranosyl chloride (Scheme 12.81). The raw material was cheap and easy to obtain, and the synthesis process was short and the operation was simple. The total yield was high to 19.6%. It was suitable for industrial production. 

Phosphonoalkyl)benzyl]guanines (246)(typical substituents R being those indicated) were synthesized by a reaction between the substituted benzyl chloride (R = Pr ) and 2-amino-6-chloropurine in the presence of CS2CO3 and examined for inhibitory properties against human erythrocyte purine nucleoside phosphorylase. The potency of the... 

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