2,6-Lutidine → HCID 70674683, compound

Participants

Reaction Steps

A solution of (S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared as in Example 1, 100 mg, 0.29 mmol,) in methylene chloride (4 mL) and N,N-dimethylformamide (4 drops) was treated with a solution of oxalyl chloride in methylene chloride (2.0 M, 150 μL, 0.30 mmol) and stirred for 15 min at room temperature. After this time, the reaction mixture was then concentrated in vacuo and the resulting residue was dissolved in methylene chloride (4 mL) and then added dropwise to a separate reaction flask containing a mixture of 3-(3-amino-pyrazol-1-yl)-propionic acid tert-butyl ester (prepared as in US 20080021032, Example 8, 92 mg, 0.44 mmol) and 2,6-lutidine (100 μL, 0.87 mmol) in methylene chloride (3 mL) at room temperature. The resulting reaction mixture was the stirred room temperature for 2 h. The reaction mixture was quenched by the addition of methanol and then diluted with methylene chloride and then washed with a 1 N aqueous hydrochloric acid solution. The organic layer was then dried over sodium sulfate, filtered and the filtrate was then concentrated in vacuo with silica gel (2.0 g). The silica gel with absorbed material was placed in a SIM and purified via Biotage flash column chromatography (40 S silica gel column, 25% ethyl acetate/hexanes) to afford 3-{3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-propionic acid tert-butyl ester (145 mg, 94%) as a white foam: HR-ES(+) m/e calcd for C27H33N4O4F3 [M+H]+ 535.2527, observed 535.2526; 1H NMR (400 MHz, DMSO-d6) δ 10.91 (s, 1H), 8.01 (dd, J=7.67, 12.79 Hz, 2H), 7.71-7.82 (m, 1H), 7.56 (d, J=2.13 Hz, 1H), 6.39 (d, J=2.13 Hz, 1H), 4.96-5.14 (m, 2H), 4.71 (d, J=18.33 Hz, 1H), 4.19 (t, J=6.50 Hz, 2H), 2.72 (t, J=6.61 Hz, 2H), 0.77-2.09 (m, 20H).

Provenance & Evidence