1-Hydroxybenzotriazole → N-[(1R)-6-[(4-Fluoro-piperidin-1-yl)-methyl]-1,2,3,4-tetrahydro-naphthalen-1-yl]-2-[2-(p-tolylsulfonyl)-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazin-1-yl]-acetamide

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Reaction Steps

DIPEA (630 μl, 3.592 mmol, 4.0 eq.) was added to a stirred solution of 2-(2-tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)acetic acid (S11) (300 mg, 0.898 mmol, 1.0 eq.) in DCM (15 ml), followed by EDCl (260 mg, 1.347 mmol, 1.5 eq.) and HOBT (183 mg, 1.347 mmol, 1.5 eq.) which were added at 0° C. The reaction mixture was allowed to stir for 30 min. A solution of R)-6-((4-fluoropiperidin-1-yl)methyl)-1,2,3,4-tetrahydronaphthalen-1-amine (A52) (0.898 mmol, 1.0 eq.) in DCM (5 ml) was added to the reaction mixture and it was stirred at RT for 16 h. The reaction mixture was diluted with DCM (50 ml) and washed with sat. NH4Cl solution (50 ml), sat. NaHCO3 solution (50 ml), water (50 ml) and brine (50 ml), and dried over Na2SO4. The solvent was evaporated under reduced pressure to give crude product which was purified by column chromatography (silica gel; 2% MeOH/DCM) to yield the desired compound as an off white solid. Yield: 38% (197 mg, 0.34 mmol); MS, Rt=3.2 min; m/z=579.1 [M H]+

Provenance & Evidence