Tetrahydrofuran → HCID 45102225, compound

Participants

Reaction Conditions

Reaction Steps

To a flame dried 50 mL round bottom flask was added the (4bR,7R,8aR)-4b-benzyl-7-hydroxy-N-(2-methylpyridin-3-yl)-6-oxo-7-phenyl-4b,5,6,7,8,8a,9,10-octahydrophenanthrene-2-carboxamide (0.28 g, 0.54 mmol) in a THF (5 mL). The solution was cooled to −17° C. in an ice/acetone bath. To the reaction was added MeLi*LiBr (0.1 mL). After 1 hour the LCMS indicated that starting material remained so an additional 0.15 mL was added. The reaction stirred to room temperature over 2 hours. By HPLC, 2.5% of the starting material remained. To the reaction was added NH4Cl slowly and off gassing was observed. The reaction was diluted to 125 mL with acetonitrile and water. The reaction was purified by reverse phase chromatography then was lyophilized. The resulting dried powder was dissolved in acetonitrile and water again with two drops of concentrated HCl. The solution was lyophilized to dryness. This afforded the title product (231.4 mg) as the HCl salt in 73% yield. LRMS ES+ 533.1 1H NMR (300 MHz, METHANOL-d4) δ ppm 1.23-1.28 (m, 3H) 1.53-1.62 (m, 1H) 1.90-2.20 (m, 3H) 2.70-2.74 (m, 3H) J=8.26 Hz, 2H) 6.84-6.92 (m, 2H) 6.99-7.10 (m, 3H) 7.13-7.29 (m, 3H) 7.45 (dd, J=8.15, 1.91 Hz, 1 H) 7.56-7.65 (m, 2H) 7.77 (d, J=1.81 Hz, 1H) 7.88 (dd, J=8.26, 5.84 Hz, 1H) 8.51-8.63 (m, 2H).

Provenance & Evidence