Reaktionsschritte
A solution of (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid (prepared as in Example 23, 79 mg, 0.25 mmol) in methylene chloride (5 mL) and N,N-dimethylformamide (5 drops) at room temperature was treated with a solution of oxalyl chloride (2.0M in methylene chloride, 150 μL, 0.30 mmol) and stirred for 15 min. After this time, the reaction mixture was concentrated in vacuo and then diluted with methylene chloride (5 mL) and added to a flask containing a solution of 5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-ylamine (prepared as in WO2004052869, Example 54, 98 mg, 0.50 mmol), 2,6-lutidine (100 μL, 0.50 mmol) in methylene chloride (2.5 mL) at room temperature. The reaction mixture was then stirred at room temperature for a period of 2 h. After this time, the reaction mixture was treated with methanol and then diluted with methylene chloride. The reaction mixture was then transferred to a separatory funnel and washed with a 1N aqueous hydrochloric acid solution. The organic layer was then dried over magnesium sulfate, filtered to remove the drying agent and the filtrate was concentrated with silica gel (2 g). The silica gel with absorbed material was placed in a SIM and purified via Biotage flash column chromatography (40 S silica gel column, 40% ethyl acetate/hexanes) to afford (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-amide (54 mg, 44%) as a colorless sticky solid: HR-ES(+) m/e calcd for C24H27N4O4F3 [M+H]+ 493.2057, observed 493.2059; 1H NMR (400 MHz, CHLOROFORM-d) δ 9.37 (d, J=1.28 Hz, 1H), 8.83 (s, 1H), 8.44 (s, 1H), 8.08 (d, J=7.46 Hz, 1H), 7.82 (d, J=7.67 Hz, 1H), 7.64 (t, J=7.78 Hz, 1H), 5.20 (t, J=6.50 Hz, 1H), 5.13 (dd, J=6.93, 8.84 Hz, 1H), 4.68-4.78 (m, 1H), 4.55-4.65 (m, 1H), 4.42 (dd, J=6.82, 8.52 Hz, 1H), 3.95 (dd, J=6.29, 8.42 Hz, 1H), 2.00-2.13 (m, 1H), 1.88-2.00 (m, 1H), 1.53-1.69 (m, 1H), 1.44-1.52 (m, 6H), 0.97-1.07 (m, 6H).
