3-Aminopropionitrile → HCID 118522810, compound

Participants

Reaction Steps

To solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-(4-oxocyclohexylidene)ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (300.0 mg, 0.569 mmol) in methanol (30 mL) was added 3-aminopropanenitrile (199.5 mg, 2.85 mmol). The resulting solution was stirred at room temperature for 3. Then NaBH3CN (71.56 mg, 1.14 mmol) was added. The resulting solution was stirred at room temperature overnight and concentrated under vacuum. The residue was applied onto a short pad of silica gel eluting with ethyl acetate. The crude product (60 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ACN/0.05% NH4HCO3=30% increasing to ACN/0.05% NH4HCO3=55% within 8 min; Detector, UV 254 nm. 6.7 mg product was obtained. This resulted in 6.7 mg (2%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(2-[4-[(2-cyanoethyl)amino]cyclohexylidene]ethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a off-white solid. LCMS (Method 34) [M+H]+=581.4, RT=2.44 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.73 (s, 1H), 9.33 (dd, 1H, J=1.5, 6.9 Hz), 8.68-8.66 (m, 2H), 8.27 (s, 1H), 7.64-7.60 (m, 2H), 7.43 (d, 1H, J=8.1 Hz), 7.27 (dd, 1H, J=4.2, 6.9 Hz), 7.00 (t, 1H, J=73.5 Hz), 5.45 (t, 1H, J=6.9 Hz), 4.80 (d, 2H, J=7.2 Hz), 2.79-2.72 (m, 3H), 2.71-2.57 (m, 5H), 2.10-1.97 (m, 2H), 1.94-1.86 (m, 2H), 1.23-1.16 (m, 2H).

Provenance & Evidence