2,6-Lutidine → (I+/-R)-I+/--(Cyclopentylmethyl)-N-[1-(2-methoxyethyl)-1H-pyrazol-3-yl]-3-methyl-4-(methylsulfonyl)benzeneacetamide

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask was placed 1-(2-methoxy-ethyl)-1H-pyrazol-3-ylamine (prepared in Example 72, 30 mg, 0.21 mmol), 2,6-lutidine (34 μL, 0.29 mmol) and methylene chloride (5 mL). This solution was then cooled to 0° C. and to it was added dropwise a solution of 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-propionyl chloride in methylene chloride (0.096 M solution, 2 mL, 0.19 mmol). The reaction was then allowed to warm up to 25° C. and stirred for 16 h. After this time the reaction was quenched with a saturated aqueous sodium bicarbonate solution (10 mL) and then extracted with methylene chloride (3×10 mL). The organic extracts were then combined and washed with a 1 N aqueous hydrochloric acid solution (1×10 mL) and then dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (4 g column, 30% ethyl acetate/hexanes to 75% ethyl acetate/hexanes) afforded 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-propionamide (57 mg, 65%) as a white foam: [α]31589=−29.5° (c=0.21, methylene chloride); ES-HRMS m/e calcd for C22H31N3O4S (M+H)+ 434.2108, observed 434.2108; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.02-1.20 (m, 2H, CH2), 1.36-1.82 (m, 8H, 4×CH2), 2.03-2.20 (m, 1H, CH), 2.62 (s, 3H, ArCH3), 3.17 (s, 3H, SO2CH3), 3.19 (s, 3H, OCH3), 3.61 (t, J=5.2 Hz, 2H, OCH2), 3.82-3.94 (m, 1H, ArCH), 4.11 (t, J=5.2 Hz, 2H, NCH2), 6.41 (d, J=2.4 Hz, 1H, Ar), 7.41-7.47 (m, 2H, Ar), 7.54 (d, J=2.4 Hz, 1H, Ar), 7.84 (d, Jo=8.8 Hz, 1H, Ar), 10.75 (s, 1H, NH).

Provenance & Evidence