Hydrochloric Acid → HCID 89908081, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide (Stage 48.1, 100 mg, 0.248 mmol), β-Alanine ethyl ester hydrochloride (267 mg, 1.736 mmol), DIPEA (0.433 mL, 2.480 mmol) and iPrOH (3 mL) were added to a vial, which was sealed and the RM was stirred at 110° C. for 44 h. The RM was treated with saturated aq. NH4Cl and extracted with EtOAc. The combined extracts were washed with sat. aq. Na2CO3 (20 mL) and brine (10 mL), dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 10). Fractions containing product were combined, treated with sat. aq. Na2CO3 and the MeCN was evaporated off under reduced pressure to give an aq. residue which was extracted with DCM and EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure. The resulting ester was dissolved in MeOH (0.5 mL) and THF (1 mL), treated with LiOH.H2O (0.548 mL, 0.548 mmol) and stirred for at RT for 90 min. The RM was acidified with aq. 1 M HCl (4 eq.) and the organic solvents were evaporated off under reduced pressure. The product was filtered off, washed with water and n-hexane and dried to give the title product as a white crystalline solid. HPLC (Condition 7) tR=6.08 min, UPLC-MS (Condition 8) tR=0.98 min, m/z=452 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.62 (t, J=6.45 Hz, 2H) 3.79 (q, J=6.26 Hz, 2H) 6.95 (s, 1H) 7.35 (d, J=8.99 Hz, 2H) 7.85-7.95 (m, J=9.38 Hz, 3H) 8.41 (d, J=1.95 Hz, 1H) 8.67 (d, J=2.35 Hz, 1H) 8.86-9.06 (m, 1H) 10.22 (s, 1H) 12.23 (br. s, 1H) 13.18 (br. s, 1H).

Provenance & Evidence