Acetonitrile → HCID 60202338, compound

Participants

Reaction Steps

A solution of the single enantiomer of 1-[5-chloro-8-(3-fluorophenyl)cinnolin-7-yl]ethanamine (400 mg, 1.3 mmol) from step O, 4-amino-6-chloropyrimidine-5-carbonitrile (250 mg, 1.6 mmol), and N,N-diisopropylethylamine (0.69 mL, 4 mmol) in 1-butanol (13 mL) was heated at 120° C. for 3 hours. The reaction mixture was concentrated and the residue was purified by RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 60 mL/min). The pure fractions were concentrated to remove all of the acetonitrile and the remaining aqueous solution was saturated with sodium bicarbonate. The aqueous solution was extracted with ethyl acetate (300 mL). The organic layer was separated, washed with brine, dried with sodium sulfate, filtered, and concentrated to give a solid. This solid was treated with acetonitrile and concentrated (2×) to give the desired product (0.25 g, 44%). LCMS for C21H16ClFN7 (M+H)+: m/z=420.1; Found: 420.1. 1H NMR (300 MHz, DMSO-d6): δ 9.48 (d, J=6.0 Hz, 1 H), 8.44 (d, J=7.8 Hz, 1 H), 8.28 (d, J=6.0 Hz, 1 H), 7.87 - 7.81 (m, 2 H), 7.61 - 7.44 (m, 2 H), 7.34 - 7.17 (m, 4 H), 5.24-5.11 (m, 1 H), 1.43 (d, J=7.0 Hz, 3 H).

Provenance & Evidence