Diisopropylamine → HCID 66668558, compound

Participants

Reaction Steps

3-(7-(4-(tert-butoxycarbonyl)piperazin-1-yl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)benzoic acid (45 mg, 0.098 mmol, 1.0 equiv), is prepared using the procedure similarly described in Example 7, is dissolved in 1 mL in dimethylformamide. To the solution is added glycine tert-butyl ester (0.016 ml, 0.118 mmol, 1.2 equiv), PyBOP (77 mg, 0.148 mmol, 1.5 equiv), then N,N-diisopropylamine (0.052 ml, 0.295 mmol, 3.0 equiv). The mixture stirred at room temperature for 18 h. Upon completion, the mixture is taken up in water and EtOAc. The layers are separated and the aqueous layer is back-extracted with EtOAc. The combined organic extracts are then washed with water twice, then brine, dried (MgSO4) and concentrated in vacuo to give a yellow oil which is purified by chromatography (silica gel, 2-5% MeOH/dichloromethane) to give tert-butyl 4-(2-(3-(2-tert-butoxy-2-oxoethylcarbamoyl)phenyl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate (41 mg, 73.0% yield) as a yellow oil. The residue is then taken on to the next reaction, which follows the same deprotection procedure as above to give 2-(3-(5-oxo-7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)benzamido)acetic acid (16 mg, 53.7% yield) as a white solid.

Provenance & Evidence