Formaldehyde → HCID 118522515, compound

Participants

Reaction Conditions

Reaction Steps

Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid {3-(5-chloro-2-difluoromethoxy-phenyl)-1-[2-(2,6-diaza-spiro[3.4]oct-2-yl)-2-oxoethyl]-1H-pyrazol-4-yl}amide (70 mg, 0.13 mmol) and paraformaldehyde (19 mg, 0.63 mmol) were stirred in 2,2,2-trifluoroethanol for 15 minutes. Sodium borohydride (14 mg, 0.38 mmol) was added and the reaction mixture was heated at 90° C. for 2 hours. The reaction mixture was allowed to cool to room temperature and was quenched with MeOH. The mixture was loaded onto an SCX-2 cartridge which had been conditioned with MeOH. After flushing with MeOH, the product was eluted with 2M ammonia in MeOH. Evaporation gave a crude product which was purified by HPLC (Method 1). The pure fractions were loaded onto an SCX-2 cartridge which had been conditioned with MeOH. After flushing with MeOH, the product was eluted with 2M ammonia in MeOH. Evaporation gave the free base which was crystallised from MeOH/Et2O. The title compound was obtained as a white solid (28 mg, 39%). LCMS (Method 5) [M+H]+=570.9, RT=2.86 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.34 (dd, 1H, J=1.5, 7.0 Hz), 8.69-8.66 (m, 2H), 8.34 (s, 1H), 8.15 (s, 1H), 7.64 (dd, 1H, J=2.7, 8.9 Hz), 7.57 (d, 1H, J=2.7 Hz), 7.47 (d, 1H, J=8.8 Hz), 7.29 (dd, 2H, J=4.3, 7.1 Hz), 7.25 (t, 1H, J=73.5 Hz), 4.94 (s, 2H), 4.04 (q, 2H, J=8.8 Hz), 3.90-3.81 (m, 2H), 2.69 (s, 2H), 2.27 (s, 3H), 2.03 (dd, 2H, J=6.8, 6.8 Hz).

Provenance & Evidence