3A Molecular sieves (10 g, 5.63 mmol) were dried under vacuum then treated with a solution of 4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidine-2-carbaldehyde (which may be prepared as described in Description 30) (1.5 g, 5.63 mmol) in dry DCM (45 mL), added under nitrogen, followed by 3-aminopyrrolidin-2-one (564.12 mg, 5.63 mmol). The mixture was gently stirred under N2 at ambient temp for 4 h. The reaction mixture was filtered through celite under suction and washed with DCM (5×20 ml). The filtrate was evaporated to an almost colourless oil which was dissolved in dry THF (60 mL) placed under nitrogen and treated with phenyl vinyl sulfone (947.7 mg, 5.6 mmol) then silver acetate (940.4 mg, 5.6 mmol). The mixture was wrapped in foil, stirred at ambient temperature for 3 minutes, then DBU (0.84 mL, 5.63 mmol) was added dropwise over a further 3 minutes and the mixture left to stir for 22 h. The reaction mixture was filtered through celite and washed through with THF (5×20 ml). The filtrate was evaporated to a dark residue, dried then dissolved in DCM (20 ml) and was applied to a 100 g silica cartridge which was initially eluted on a Biotage SP4 system with a gradient of methanol in ethyl acetate, then finally with 1M NH3-MeOH:EtOAc 1:9 to give 2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]-pyrimidin-2-yl]-1,7-diazaspiro[4.4]non-1-en-6-one (D31) (774 mg);
