Hydrochloric Acid → HCID 178463541, compound

Participants

Reaction Conditions

Reaction Steps

A solution of the single enantiomer of 1-[5-chloro-8-(3-fluorophenyl)cinnolin-7-yl]ethanamine (0.52 g, 1.7 mmol) from Step B, 6-bromo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (0.73 g, 2.6 mmol), and N,N-diisopropylethylamine (0.90 mL, 5.1 mmol) in ethanol (9 mL) was heated at 90° C. for 21 hours. The reaction mixture was concentrated to give the crude THP-purine intermediate which was used without further purification. A solution of this material in methanol (10 mL) was treated with 1 M hydrogen chloride in water (15 mL, 15 mmol) and stirred at 20° C. for 1 hour. The reaction mixture was concentrated and purified by RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 60 mL/minute). The pure fractions were neutralized with ammonium hydroxide to pH˜7 and concentrated to remove all of the acetonitrile and most of the water. The solid that precipitated was filtered, washed with water, and dried to give the desired product (0.44 g, 62%). % ee>99.9. LCMS for C21H16ClFN7 (M+H)+: m/z=420.1; Found: 419.9. 1H NMR (300 MHz, DMSO-d6): δ 12.9 (br s, 1 H), 9.47 (d, J=5.9 Hz, 1 H), 8.50-8.38 (m, 2H), 8.26 (d, J=5.9 Hz, 1 H), 8.14 (br s, 1 H), 8.06 (d, J=10.8 Hz, 1 H), 7.64-7.52 (m, 2H), 7.37-7.22 (m, 2H), 5.36 (br s, 1H), 1.48 (d, J=6.7 Hz, 3H).

Provenance & Evidence