Diisopropylethylamine → HCID 178463529, compound

Participants

Reaction Conditions

Reaction Steps

To a reaction flask containing 1-(6-(pyridin-2-yl)thieno[2,3-b]pyridin-5-yl)ethanamine (134 mg, 0.525 mmol), 6-chloropurine (97 mg, 0.63 mmol, 1.2 eq) and diisopropylethylamine (137 μL, 0.79 mmol, 1.5 eq) was added 5 mL of n-butanol. The reaction was heated to 110° C. for 24 h, then cooled to rt and concentrated in vacuo. The residue was dissolved in ethyl acetate (˜50 mL) with heat and sonication, then washed with 5 mL water and 5 mL brine. The organic layer was dried over MgSO4, filtered, and concentrated. Purification by column chromatography using 0-80% gradient of (90:9:1 DCM:MeOH:NH4OH) in dichloromethane afforded racemic N-(1-(6-(pyridin-2-yl)thieno[2,3-b]pyridin-5-yl)ethyl)-9H-purin-6-amine. The room temperature NMR spectrum in CDCl3 exists as a roughly 3:1 mixture of isomers. 1H NMR (400 MHz, CDCl3) δ 8.80 (br d, J=4.3 Hz, 0.75 H), 8.73 (br d, J=3.1 Hz, 0.25 H), 8.55 (s, 0.25 H), 8.36-8.26 (series of m, 1.75 H), 8.15-8.03 (series of m, 1.5 H), 7.93 (br s, 0.75 H), 7.88 (m, 1.4 H), 7.56 (m, 0.5 H), 7.55 (d, J=5.9 Hz, 0.75 H), 7.37 (dd, J=6.6, 5.1 Hz, 0.75 H), 7.26 (d, J=5.9 Hz, 0.75 H), 7.20 (d, J=5.9 Hz, 0.25 H), 6.65 (m, 0.25 H), 6.35 (m, 0.25 H), 6.15 (br s, 0.75 H), 1.55 (d, J=7.0 Hz, 2.25 H), 1.35 (d, J=6.3 Hz, 0.75 H) ppm. LC/MS (M+1, found=374.0). Chiral SFC separation of the racemate afforded the individual enantiomers, (S)—N-(1-(6-(pyridin-2-yl)thieno[2,3-b]pyridin-5-yl)ethyl)-9H-purin-6-amine and (R)—N-(1-(6-(pyridin-2-yl)thieno[2,3-b]pyridin-5-yl)ethyl)-9H-purin-6-amine.

Provenance & Evidence