Triethylamine → (S)(-)-2-(7-chloro-6-fluoro-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)phenyl]ethyl}acetamide

Participants

Reaction Steps

A mixture of (7-chloro-6-fluoro-1H-benzimidazol-1-yl)acetic acid (1.00 g, 4.39 mmol) prepared according to scheme 12, (S)(−)-2-{4-[1-aminoethyl]phenyl}-2-methylpropanenitrile (825 mg 4.39 mmol) prepared according to scheme 20 or 21 and Et3N (1.33 g, 13.2 mmol, 1.84 mL) is stirred in MeCN (50.0 mL). HATU (1.67 g, 4.39 mmol) is added, and, after 2 hours of stirring, the mixture is diluted with 1N NaOH (100 mL) and then extracted 4 times with EtOAc (4×75.0 mL). The organic phases are combined and dried over Na2SO4. The mixture is filtered and concentrated. The product is purified by a Gilson prep pump, flow rate: 30 ml/min, column: Gemini™ (5u) 21.2×50 mm, mobile phase: A=10 mM ammonium bicarbonate, B=MeCN (1.01 g, 58%). 1H NMR (400 MHz, DMSO-D6) δ ppm 1.39 (d, J=7.03 Hz, 3H) 1.66 (s, 6H) 4.92 (quint, J=7.23 Hz, 1H) 5.19 (s, 2H) 7.23 (dd, J=10.16, 8.98 Hz, 1H) 7.37 (d, J=8.20 Hz, 2 H) 7.47 (d, J=8.59 Hz, 2H) 7.63 (dd, J=8.79, 4.49 Hz, 1H) 8.21 (s, 1H) 8.81 (d, J=7.81 Hz, 1 H) MS [M+H], calcd: 399.1. found: 399.2, [α]D=−165 (c=1.02 METHANOL) HRMS (ESI+) calcd for C21H21ClFN4O 399.13824 [M+H]+ found 399.13832.

Provenance & Evidence