Triphenylphosphine → 1-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridine

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

(3 aS,4S,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (1-3) (4.3 g, 27.2 mmol, 1 equiv) was dissolved in dry THF (136 mL). Triphenylphosphine (10.7 g, 40.8 mmol, 1.5 equiv) was added, followed by 4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-4, 5.1 g, 32.6 mmol, 1.2 equiv). The mixture was cooled to 0° C. and DIAD (7.9 mL, 40.8 mmol, 1.5 equiv) was added dropwise. The resulting mixture was stirred at ambient temperature for 14 hours and then heated to 50° C. for an additional 72 hours. The solvent was removed at reduced pressure and the yellow residue was purified via flash chromatography on 2-330 g silica gel columns (gradient elution 0 to 100% ethyl acetate in hexanes) to yield 1-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-6) and 3-((3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4,7-difluoro-3H-imidazo[4,5-c]pyridine (1-5) as a 1:1 regioisomeric mixture. 1H NMR (1-6) (500 MHz, CDCl3): δ 7.85 (m, 2H); 5.00 (brs, 1H); 4.90 (t, J=5.6 Hz, 1H); 4.82 (t, J=7.3 Hz, 1H); 2.56 (m, 1H); 2.04-2.19 (m, 3H); 1.55 (s, 3H); 1.34 (s, 3H). LRMS rn/z (M+H) 296.0 found, 296.1 required. 1H NMR (1-5) (500 MHz, CDCl3): δ 7.92 (s, 1H); 7.82 (m, 1H); 5.00 (brs, 1H); 4.90 (t, J=5.6 Hz, 1H); 4.82 (t, J=7.3 Hz, 1H); 2.56 (m, 1H); 2.04-2.19 (m, 3H); 1.55 (s, 3H); 1.34 (s, 3H). LRMS m/z (M+H) 296.0 found, 296.1 required.

Herkunft & Nachweise