2-Thiophenecarboxylic acid → US9296747, Example 13

Participants

Reaction Steps

A solution of (Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (0.021 g, 0.047 mmol) in anhydrous DMF (1.5 mL) was treated sequentially with thiophene-2-carboxylic acid (0.008 g, 0.062 mmol) and diisopropylethylamine (0.025 mL, 0.095 mmol). The reaction mixture was allowed to stir for 30 minutes at room temperature. After 30 minutes, N-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine, Intermediate 1 (0.015 g, 0.047 mmol) was added to the reaction mixture. The reaction was allowed to stir for 3 hours at room temperature. The reaction mixture was then diluted with EtOAc and washed three times with brine. The combined aqueous layers were then washed twice with EtOAc. The organic layers were combined, dried over anhydrous Na2SO4(s), filtered and concentrated in vacuo. The crude product was then purified over silica using a MeOH/CHCl3 gradient affording the final product in 40% yield (0.008 g, 0.019 mmol).

Provenance & Evidence