Sodium hydride → 5-(4-(((4-methoxybenzyl)oxy)methyl)thiazol-2-yl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Participants

Reaction Steps

Sodium hydride (60% wt, 0.637 g, 15.93 mmol) was added portionwise to a solution of 5-(4-(hydroxymethyl)thiazol-2-yl)-1,3-dimethyl-6-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (step 2) (4.43 g, 7.97 mmol) NMP (Volume: 44 ml) at 0° C. and stirred for 1 hour. para-Methoxybenzyl chloride (1.404 ml, 10.36 mmol) was added and the mixture stirred at room temperature for 5 hours. Further portions of para-methoxybenzyl chloride (220 μl) and sodium hydride (60% wt, 64 mg) were added and the mixture stirred for a further 16 hours. The reaction was quenched at 0° C. with saturated NaHCO3(aq) (50 ml), diluted with water (200 ml) and EtOAc (100 ml) and the phases separated. The aqueous phase was extracted with EtOAc (3×100 ml). The combined organic extracts were washed with water (2×100 ml) and brine (100 ml), dried over sodium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 40-60% EtOAc/hexane afforded the title compound and 5-(4-(((4-methoxybenzyl)oxy)methyl)thiazol-2-yl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione as a mixture which was used without further purification.

Provenance & Evidence