Carbonic acid--N,N-diethylethanamine (1/2) → HCID 68052028, compound

Participants

Reaction Steps

To the product of Step 1 (7.56 g, 18.7 mmol) was added water (100 mL). The solution was then sonicated and gently warmed to ensure complete dissolution of the starting material. To the light brown solution was added Biotage MP-carbonate resin (30 g, 3.34 mmol/g). The solution was swirled gently for 16 hours before being filtered through a thin pad of Celite which was rinsed with acetonitrile and water successively. The filtrate was concentrated in vacuo, azeotroped with toluene (twice), then azeotroped with methanol (twice). The resulting light brown solid was dissolved in methanol (40 mL) and separated by preparative SFC using a ChiralPak IA column (50×250 mm) with 35% modifier solution comprised of methanol with 0.2% diethylamine at 250 mL/min (enantiomer retention times=3.4 minutes {enantiomer 1}& 4.7 minutes {enantiomer 2}). Concentration of the separated enantiomer solutions gave 98.2% ee material for enantiomer 1 (retention time=3.4 minutes) and 94.6% ee for enantiomer 2 (retention time=4.7 minutes). LRMS calc'd for C13H18N5 [M+H]+, 244; found 244. 1H NMR (500 MHz, CD3OD) δ 8.05 (s, 1H), 7.06 (d, J=3.6Hz, 1H), 6.58 (d, J=3.5 Hz, 1H), 4.27 (m, 1H), 3.96 (m, 1H), 3.80 (m, 1H), 3.56 (m, 1H), 2.82-2.73 (m, 2H), 2.36 (m, 1H), 2.25 (m, 1H), 2.00 (m, 1H), 1.63-1.46 (m, 3H). Enantiomer 1 Jak1 activity: +; Enantiomer 2 Jak1 activity: +.

Provenance & Evidence