Sodium Bicarbonate → 8-(6-(1H-pyrrol-3-yl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amine

Participants

Reaction Conditions

Reaction Steps

9-(3-(isopropylamino)propyl)-8-(6-(isoxazol-4-yl)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine [DZ3-49]. 4-Isoxazoleboronic acid pinacol ester (20.5 mg, 0.1053 mmol) was added to PU-H71 (30 mg, 0.0585 mmol) and NaHCO3 (14.7 mg, 0.1755 mmol). DMF (1.2 mL) was added and the reaction mixture was evacuated and back filled with nitrogen. This was repeated four times then nitrogen was bubbled through the reaction mixture for 10 minutes. Then H2O (0.1 mL) and Pd(PPh3)2Cl2 (8 mg, 0.0117 mmol) were added and the reaction mixture was heated under nitrogen at 60° C. for 4 h. Solvent was removed under reduced pressure and the resulting residue was attempted to be purified by preparatory TLC (hexane:CH2Cl2:EtOAc:MeOH—NH3 (7N), 4:7:2:1) to give 7.4 mg (28%) of an inseparable mixture of DZ3-49 and DZ3-39 in a ratio of approximately 71:29, respectively, as determined by HPLC. 1H NMR (500 MHz, CDCl3/MeOH-d4) δ 8.66 (s, 1H), 8.45 (s, 1H), 8.17 (s, 1H), 7.18 (s, 1H), 7.01 (s, 1H), 6.13 (s, 2H), 4.37 (t, J=7.0 Hz, 2H), 3.27 (septet, J=7.1 Hz, 1H), 2.89 (t, J=7.1 Hz, 2H), 2.22 (m, 2H), 1.38 (d, J=6.5 Hz, 6H); MS (ESI) m/z [M+H]+ 454.1; HPLC: method ARt=5.67 (DZ3-39, 29%) and 5.87 (DZ3-49, 71%); method B Rt=4.58 (DZ3-39, 34%) and 5.57 (DZ3-49, 66%).

Provenance & Evidence