Hydrochloric Acid → HCID 74983213, compound

Participants

Reaction Conditions

Reaction Steps

To a solution/suspension of tert-butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)cycloheptyl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate (Diastereomer 1) (49 mg, 0.074 mmol) in MeOH (2 mL) was added a solution of HCl in dioxane (4 M, 1.9 mL, 7.42 mmol) and the mixture was heated at 60° C. for 72 hr. The solvent was removed under reduced pressure and the residue was dissolved in MeOH/water (5 mL/5 mL) and treated with K2CO3 (51 mg, 0.37 mmol). The mixture was heated at 65° C. for 18 hr. The MeOH was removed under reduced pressure and the aqueous residue was extracted with 5% MeOH/DCM (2×30 mL). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure. The residue was dissolved in MeOH and loaded onto an SCX column. The column was washed with MeOH, eluted with 3 N ammonia in MeOH and the solvent removed under reduced pressure to give 357 (Diastereomer 1) as a beige solid (10 mg, 29% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.76 (s, 1H), 7.35-7.28 (m, 1H), 7.07-6.99 (m, 2H), 6.11 (s, 2H), 4.46-4.29 (m, 1H), 3.83 (s, 3H), 3.23-3.13 (m, 1H), 2.84-2.76 (m, 1H), 2.26-1.81 (m, 6H), 1.60-1.40 (m, 2H). Alkyl NH2 not observed. LCMS (ES+) m/z 465 (M+1)

Provenance & Evidence