Ammonia → N2 (4-fluorophenylacetyl)-guanosine

Participants

Reaction Steps

Guanosine 5 (7.08 g, 25 mmoles) was dried three times by coevaporation with dried pyridine and suspended in 140 ml of dry pyridine. To this was added trimethylsilyl chloride (24 ml, 180 mmoles) at room temperature. After the solution was stirred for 1 hour at room temperature, 4-fluorophenylacetyl chloride (13.9 g, 80 mmoles) was added dropwise and the solution stirred for 15 hours. The reaction mixture was then cooled in an ice bath and 20 ml of cold water was added. After 30 minutes 20 ml of 29% aqueous ammonia was added and the mixture stirred for 30 minutes. The solution was then evaporated to near dryness and the residue dissolved in 300 ml water and 300 ml methylene chloride. The product crystallized out of the solution upon extraction with CH2Cl2 was filtered off, washed with CH2Cl2 (3×70 ml) and ether (5×70 ml) and air dried to yield 6 g (57%) of Ribo GFPA 6b. The product was characterized as following: m.p. 160°-170° C. (dec.); UV (EtOH): λ max 280 nm and 258 nm; IR (KBr): ν 1687 (vs, br, C=O of amides), 3000-3500 (NH, OH) cm-1. 1H-NMR (DMSO-d6): δ 3.36 (m, 2H, C5, CH2), 3.79 (s, 2H, CH2C6H4), 3.91(m, 1H, C4, H), 4.13 (m, 1H, C3, H), 4.42(m, 1H, C2, H), 5.81 (t, 1H, J1',2' =5.64 Hz, C1, H), 7.15-7.37 (m, 4H, C6H4), 8.27 (d, 1H, C8H), 11.91 and 11.97 (2s, 2H, 2×NHCO).

Provenance & Evidence