Synthesis of imidazo[4,5-b]pyridines and v-triazolo[4,5-b]pyridines. Preparation of 1-deaza-6-thioguanine analogs

Synthesis of 1-deaza-6-thioguanosine and 1-deaza-6-(methylthio)guanosine

“…The mixture was cooled to 25 °C, filtered, and evaporated to dryness in vacuo. A solution of the residue in benzene (25 mL) was filtered and evaporated to give 1.53 g of crude 6 which was dissolved in CHC13, applied to eight preparative TLC plates, and developed with CHC13-CH30H (95:5). The major band was extracted with CHC13-CH30H (1:1) and evaporated to dryness in vacuo.…”

“…The major band was extracted with CHC13-CH30H (1:1) and evaporated to dryness in vacuo. A solution of the residue in CHC13 (10 mL) was filtered and evaporated to give 1.04 g of 6 as a foam containing only minor traces of impurities (TLC): NMR 2.02-2.16 (m, Ac), 4.08-4.5 (m, 3, CH2, H4-), 5.59 (d, 1, H3,), 6.00 (t, 1, H2-), 6.29 (d, 1, JV2-= 3.0 Hz, Hr), 8.24, 8.69 (s, s, 2, H2, H6), 10.65 (s, 1, NH). A solution of 6 and NaOMe (0.52 g, 9.62 mmol) in MeOH (200 mL) was stirred at 62 °C for 16 h, cooled to 25 °C, neutralized with Amberlite IR-120 H+ ion-exchange resin, and filtered and the resin was extracted with MeOH and H20.…”

“…The reported antitumor activity of 6-thioguanine1 and the nucleosides 6-thio-2,3 and 6-(methylthio)guanosine4 prompted our invesigation of synthetic routes to 5amino-3,4-dihydro-3-/3-D-ribofuranosyl-7fl-imidazo [4,[5][6]pyridine-7-thione (l-deaza-6-thioguanosine, 8) and 7-(methylthio)-3-,8-D-ribofuranosyl-3fí-imidazo[4,5-í>]pyridin-5-amine [l-deaza-6-(methylthio)guanosine, 9].…”

“…An initial attempt was made to prepare 9 by a nucleoside coupling reaction between JV-acetyl-7-(methylthio)-lHimidazo [4,[5][6]pyridin-5-amine (2) and 2,3,5-tri-Oacetyl-D-ribofuranosyl chloride5 (3). Acetylation of 7-(methylthio)-lfí-imidazo [4,pyridin-5-amine6 (1) in refluxing acetic anhydride gave 2 which was heated with 3 in 1,2-dichloroethane at 75 °C in the presence of Linde 4A molecular sieve for 6 days.…”

“…The successful route to 8 and 9 involved nucleophilic displacement of the chlorine from 7-chloro-3-d-D-ribofuranosyl-3//-imidazo [4,pyridin-5-amine (7). 7-Chloro-l/i-imidazo [4,[5][6]pyridin-5-amine7 (4) was treated with acetic anhydride to give a diacetylation product which was partially hydrolyzed to give the monoacetyl derivative 5.…”