4H-Pyrrolo[3,2-d]pyrimidin-4-one, 2-amino-1,5-dihydro- (9CI)

Beige Solid

2-Amino-3H-pyrrolo[3, 2-]pyrimidm-4(5H)-one To a mixture of 2-amino-3-benzyl-3H-pyrrolo[3, 2-(f]pyrimidin-4(5H)-one (10 g, 0.04 mol) in MeOH (334 mL) was added 10percent Pd/C (2 g), ammonium formate (13.2 g, 0.21 mmol) and heated at 75A mixture of 10 (24 g) and sodium dithionite (48 g) in water (240 ml) was heated under reflux for 2 h.. Preparation of Intermediate DDTo a mixture of Intermediate CC (200 mg, 1.049 mmol), EtIn the sequence, in a microwave tube was added 4 (200 mg, 0.97 mmol) and NaOH (195.0 mg, 4.84 mmol) in H2O (5 mL). Theset conditions were 95 C for 15 min with an average power of40 W. This procedure was repeated four times and then the crudeproducts were mixed. The solvent was evaporated under vacuumand then water (5 mL) was added. The mixture was acidified topH 5.0 with glacial acetic acid. The precipitate was filtered andthen recrystallized in ethanol/H2O (3:1) affording the desired product5 in 96percent yield (701.0 mg)General procedure: Amixture of 9-deazapurine 5 (150.0 mg, 1.0 mmol) and benzoylchloride (2.2 equiv) in trifluoromethanesulfonic acid (3.45 g, 23 mmol) was stirred at 80-120 C for 48 h. After the mixturewas cooled and H2O (15 mL) was added. Then the reaction wasneutralized with NaOH 1.0 mol/L, the volume adjusted to approximately35 mL by adding H2O and then 60 equiv of NaOH wereadded. The reaction was stirred for 2.5 h at 60 C. The mixturewas neutralized with glacial acetic acid and the formed solid wasfiltered under vacuum and washed several times with dichloromethane(10 mL), ethyl acetate (10 mL), acetone (5 mL) andmethanol (5 mL). The precipitate purity was monitored by CCDand depending on the product, further purification was necessaryby recrystallization in methanol or flash chromatography usingCH2Cl2/MeOH (4:1) as eluent.General procedure: Amixture of 9-deazapurine 5 (150.0 mg, 1.0 mmol) and benzoylchloride (2.2 equiv) in trifluoromethanesulfonic acid (3.45 g, 23 mmol) was stirred at 80-120 C for 48 h. After the mixturewas cooled and H2O (15 mL) was added. Then the reaction wasneutralized with NaOH 1.0 mol/L, the volume adjusted to approximately35 mL by adding H2O and then 60 equiv of NaOH wereadded. The reaction was stirred for 2.5 h at 60 C. The mixturewas neutralized with glacial acetic acid and the formed solid wasfiltered under vacuum and washed several times with dichloromethane(10 mL), ethyl acetate (10 mL), acetone (5 mL) andmethanol (5 mL). The precipitate purity was monitored by CCDand depending on the product, further purification was necessaryby recrystallization in methanol or flash chromatography usingCH2Cl2/MeOH (4:1) as eluent.General procedure: Amixture of 9-deazapurine 5 (150.0 mg, 1.0 mmol) and benzoylchloride (2.2 equiv) in trifluoromethanesulfonic acid (3.45 g, 23 mmol) was stirred at 80-120 C for 48 h. After the mixturewas cooled and H2O (15 mL) was added. Then the reaction wasneutralized with NaOH 1.0 mol/L, the volume adjusted to approximately35 mL by adding H2O and then 60 equiv of NaOH wereadded. The reaction was stirred for 2.5 h at 60 C. The mixturewas neutralized with glacial acetic acid and the formed solid wasfiltered under vacuum and washed several times with dichloromethane(10 mL), ethyl acetate (10 mL), acetone (5 mL) andmethanol (5 mL). The precipitate purity was monitored by CCDand depending on the product, further purification was necessaryby recrystallization in methanol or flash chromatography usingCH2Cl2/MeOH (4:1) as eluent.

A nucleoside analog as potent inhibitor of purine nucleoside phosphorylase.