Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (-)-2-(7-Cyano-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)-3-methylphenyl]ethyl}acetamide

Participants

Reaction Steps

To a solution of (7-cyano-1H-benzimidazol-1-yl)acetic acid (100 mg, 0.50 mmol) prepared according to scheme 3, 2-{4-[1-aminoethyl]-2-methylphenyl}-2-methylpropanenitrile (101 mg, 0.50 mmol) prepared according to scheme 16 and DMAP (120 mg, 1.00 mmol) stirred in anhydrous DMF (2.0 mL) is added HATU (189 mg, 0.50 mmol) after 18 hours of stirring, the mixture is diluted with Methanol (200 μL) the solution is purified directly on a preparative on a preparative LCMS system equipped with a Synergi Polar (4u) 21.2×50 mm column, mobile phase: A=water (0.1% TFA), B=MeCN using a short 40 to 60% B 10 min. gradient method. The pure fractions are combined the TFA neutralized with a 4N NaOH solution and then extracted with ethyl acetate which is separated dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide the expected product (+) and (−)-2-(7-Cyano-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)-3-methylphenyl]ethyl}acetamide (143 mg, 75%) as a white solid. 1H NMR (400 MHz, METHANOL-D4) δ ppm 1.49 (d, J=7.03 Hz, 3H) 1.75 (s, 6H) 2.61 (s, 3H) 4.99 (q, J=7.03 Hz, 1H) 5.28-5.40 (m, 2H) 7.21-7.29 (m, 2H) 7.33 (d, J=8.20 Hz, 1H) 7.37-7.44 (m, 1H) 7.69 (dd, J=7.42, 0.78 Hz, 1H) 7.98 (dd, J=8.20, 1.17 Hz, 1H) 8.27 (s, 1H) MS [M+H], calcd: 386.2. found: 386.2.

Provenance & Evidence