2-Bromo-4-chloro-1,3-thiazole → 3-(6-(4-(4-Chlorothiazol-2-yl)-4-oxobutyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)benzonitrile

Participants

Reaction Conditions

Reaction Steps

Isopropylmagnesium chloride lithium chloride complex solution (1.3 M in THF, 2.067 ml, 2.69 mmol) was added dropwise to a solution of 4-(5-(3-cyanophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)-N-methoxy-N-methylbutanamide (1 g, 2.442 mmol) and 2-bromo-4-chlorothiazole (Intermediate Q, step 2) (0.533 g, 2.69 mmol) in THF (24.42 mL) at 0° C. The mixture was stirred at 0° C. for 30 minutes. A further portion of isopropylmagnesium chloride lithium chloride complex solution (1.3 M in THF, 2.067 ml, 2.69 mmol) was added at 0° C. and the mixture was stirred for a further 30 minutes at 0° C. The reaction was quenched with saturated NH4Cl(aq) (20 mL) and extracted with DCM (3×20 mL). The combined organic extracts were washed with saturated NaHCO3(aq) (10 mL), dried over magnesium sulfate and evaporated under reduced pressure. Trituration with methanol afforded the title compound.

Provenance & Evidence