Dichloromethane → HCID 67188673, compound

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask under argon was placed triphenylphosphine (120 mg, 0.46 mmol) and methylene chloride (10 mL) and it was cooled to 0° C. in an ice bath. To this was added N-bromosuccinimide (81 mg, 0.46 mmol) and it was stirred for 15 minutes at 0° C. To this was then added 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionic acid (prepared as in PCT WO 2002/046173 A1, Example 3, 100 mg, 0.35 mmol) and it was stirred for an additional 5 minutes at 0° C. and then warmed to 25° C. and stirred for 10 minutes. The solution was recooled to 0° C. and then 1-methyl-1H-pyrazol-3-ylamine (68 mg, 0.70 mmol) in methylene chloride (500 μL) and 2,6-lutidine (160 μL, 1.4 mmol) were added to the flask and it was stirred at 0° C. and then warmed to 25° C. and stirred for 2.5 h. After this time the reaction was diluted with methylene chloride and then washed with an aqueous 1 N hydrochloric acid solution and saturated aqueous brine solution. Flash chromatography using Biotage system (40S column, Silica gel, 50% ethyl acetate/hexanes) provided a white foam, this material was then lyophilized to afford 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-(1-methyl-1H-pyrazol-3-yl)-propionamide (62 mg, 48%) as a white powder: [α]27589=−15.6° (c=0.27, methanol); ES-HRMS m/e calcd for C18H21N30Cl2 (M+H)+ 366.1135, observed 366.1135; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.01-1.19 (m, 2H, CH2), 1.34-1.80 (m, 8H, 4×CH2), 1.95-2.14 (m, 1H, CH), 3.70 (s, 3H, NCH3), 3.79 (dd, J=8.6, 6.0 Hz, 1H, ArCH), 6.30-6.44 (m, 1H, Ar), 7.34 (dd, Jo=8.4 Hz, Jm=1.3 Hz, 1H, Ar), 7.51 (d, Jm=1.3 Hz, 1H, Ar), 7.54-7.65 (m, 2H, Ar), 10.66 (s, 1H, NH).

Provenance & Evidence