Diisopropylethylamine → 2-(2-Tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)-N-((R)-6-((2,2,2-trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide

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Reaction Steps

To a solution of 2-(2-tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)acetic acid (S11) (214 mg, 0.64 mmol, 1.0 eq.) in THF (5 ml) were added DIPEA (340 μl, 1.92 mmol, 3.0 eq.) and HATU (292 mg, 0.77 mmol, 1.2 eq.) at 0° C. and the mixture was stirred for 15 min at the same temperature. A solution of (R)-6-((2,2,2-trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-amine (A53) (0.64 mmol, 1.0 eq.) in THF (5 ml) was added to the reaction mixture and it was stirred at RT for 16 h. The reaction mixture was concentrated and the residue was diluted with DCM (50 ml) and washed with sat. NH4Cl solution (20 ml), sat. NaHCO3 solution (20 ml), water (20 ml) and brine (20 ml). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 0.7% MeOH/DCM) to yield the desired product as an off-white solid. Yield: 22% (80 mg, 0.14 mmol); MS, Rt=3.2 min; m/z=575.0 [MH]+

Provenance & Evidence