N,N-Dimethylglycine → 4-Cyano-1h-pyrrole-2-carboxylic acid (2-cyclohex-1-enyl-4-[1-(2-dimethylamino-acetyl)-piperidin-4-yl]-phenyl)-amide trifluoroacetic acid salt

Participants

Reaction Steps

A suspension of 9.10 mg (0.0881 mmol) dimethylamino-acetic acid in 5 mL CH2Cl2 was treated with 21.7 mg (0.0852 mmol) BOP—Cl and 32.8 μL (0.235 mmol) triethylamine at RT for 50 min. This mixture was added to a suspension of 22.0 mg (0.0588 mmol) 4-cyano-1H-pyrrole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide trifluoroacetic acid salt (as prepared in the previous step) in 5 mL CH2Cl2. The mixture stirred at RT for 23 h, was diluted with CH2Cl2 (15 mL), and washed with saturated aqueous NaHCO3 (1×10 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Purification of the residue by RP-HPLC (C18) with 20-80% CH3CN in 0.1% TFA/H2O over 30 min to afford 33.6 mg (83%) of the title compound as a white solid: 1H-NMR (CD3OD; 400 MHz): δ 7.54 (d, 1H, J=1.6 Hz), 7.41 (d, 1H, J=8.0 Hz), 7.14 (dd, 1H, J=8.4 Hz, J=2.0 Hz), 7.12-7.08 (m, 1H), 7.07 (d, 1H, J=2.0 Hz), 5.70-5.65 (m, 1H), 4.67-4.59 (m, 1H), 4.26 (q, 2H, J=16.4 Hz), 3.78-3.70 (m, 1H), 3.26-3.17 (m, 1H), 2.97-2.89 (m, 6H), 2.88-2.75 (m, 2H), 2.25-2.18 (m, 2H), 2.15-2.07 (m, 2H), 1.94-1.85 (m, 2H), 1.76-1.54 (m, 6H). Mass spectrum (ESI, m/z): Calcd. for C27H33N5O2, 460.3 (M+H), found 460.3.

Provenance & Evidence