Dimethylformamide → HCID 18002307, Verbindung

Beteiligte Stoffe

Reaktionsschritte

(3Z)-3-(3,5-Dimethyl-4-carboxy-1H-pyrrol-2-ylmethylidene)-5-fluoro-1,3-dihydro-2H-indol-2-one (120 mg, 0.40 mmol), prepared as described in published PCT Application WO01/60814, and BOP (221 mg, 0.50 mmol) were suspended in DMF (5 mL) with good stirring at room temperature and triethylamine (134 μL, 0.96 mmol) was added. After 10-15 min., to the homogeneous reaction mixture was added the 4-(morpholin-4-yl)piperidine (85 mg, 0.50 mmol) all at once. The reaction mixture was stirred for 48 h (might be done much earlier), then transferred to a funnel containing chloroform-isopropanol (5/1) and 5% aq. LiCl. The cloudy-orange organic phase was separated, washed with additional 5% aq LiCl (2×), 1 M aq NaOH (3×), satd aq NaCl (1×), and then dried (Na2SO4) and evaporated to yield the crude product (96.3% pure; trace hexamethylphosphoramide (HMPA) by 1HNMR). This crude product was then further purified by passage through a very short column (3 cm) of silica gel (5 to 15% gradient of MeOH in dichloromethane (DCM)) where a trace of faster moving 3E-isomer was removed. The pure fractions were evaporated and recrystallized overnight from a satd EtOAc soln which was diluted with Et2O (˜3-fold) and chilled at 0° C. The mother liquor was decanted to yield after full vacuum the desired compound as orange crystals (153 mg 85%).

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