Triethylamine → (-) 2-(7-chloro-6-fluoro-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)-3-fluorophenyl]ethyl}acetamide

Participants

Reaction Steps

A mixture of (7-chloro-6-fluoro-1H-benzimidazol-1-yl)acetic acid (210 mg, 0.921 mmol) prepared according to scheme 12, 2-{4-[1-aminoethyl]-2-fluorophenyl}-2-methylpropanenitrile (190 mg 0.921 mmol)) prepared according to scheme 7 and Et3N (280 mg, 2.76 mmol, 0.39 mL) is stirred in MeCN (10.0 mL). HATU (350 mg, 0.921 mmol) is added, and after 2 hours of stirring, the mixture is diluted with 1N NaOH (40.0 mL) and then extracted 4 times with EtOAc (4×40.0 mL). The organic phases are combined and dried over MgSO4. The mixture is filtered and concentrated. The product is purified by a Gilson prep pump, flow rate: 30 ml/min, column: Synergi Polar (4u) 21.2×50 mm, mobile phase: A=water (0.1% TFA), B=MeCN (206 mg, 54%). 1H NMR (400 MHz, DMSO-D6) δ ppm 1.38 (d, J=6.84 Hz, 3H) 1.71 (s, 6H) 4.85-5.00 (m, J=7.13, 7.13 Hz, 1H) 5.21 (s, 2H) 7.15-7.31 (m, 3H) 7.42 (t, J=8.30 Hz, 1H) 7.63 (dd, J=8.89, 4.39 Hz, 1H) 8.21 (s, 1H) 8.84 (d, J=7.81 Hz, 1H). The enantiomers are separated on a chiral AD column, eluting with 30% EtOH (0.1% DIEA) and hexanes 70% (0.1% DIEA), MS [M+H], calcd: 417.1. found: 417.3 [α]D=+154 (c=13, MeOH) and [α]D=−155 (c=15, MeOH).

Provenance & Evidence