Morpholine → HCID 59395729, compound

Participants

Reaction Steps

A solution of 5-benzyl-1H-tetrazole (1.0 g, 6.24 mmol) in MeOH (5 ml) was treated with 1-chloro-3-iodopropane (1.0 ml, 9.36 mmol) and a solution of 0.5M NaOMe in MeOH (4.7 ml, 9.36 mmol). The reaction was heated at reflux for 18 h then partitioned between 2M HCl (aq) and EtOAc. The organic layer was separated and the aqueous layer extracted once more with EtOAc. The combined extracts were washed with brine, dried (MgSO4) and concentrated, giving a yellow solid. (796 mg). 700 mg of this material was reacted with 8-chloro-3-pentyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (732 mg, 2.47 mmol) and Cs2CO3 (967 mg, 3.0 mmol) in DMF (20 ml) at 75° C. for 24 h. The reaction was allowed to cool to rt and the mixture was degassed by applying a vacuum and then nitrogen was introduced. Pd(PPh3)4 (428 mg, 0.37 mmol) was added and the mixture degassed once more. Morpholine (2.1 ml, 24.7 mmol) was added and the mixture was stirred under nitrogen for 3 h, then partitioned between 2M HCl (aq) and EtOAc. The organic layer was separated and the aqueous layer extracted once more. The combined extracts were concentrated, giving a yellow residue. MeOH was added and then passed down an aminopropyl SPE, the product eluting with 2-3% AcOH/MeOH. The product fractions were combined and concentrated then purified by the MDAP to give the title compound as a white solid (35 mg, 3%).

Provenance & Evidence