Acetic Acid → HCID 16225381, compound

Participants

Reaction Steps

To a reaction vessel charged with 1-methyl-1H-pyrazole-4-carboxaldehyde (84.5 mg, 0.77 mmol) was added a solution of tert-butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate (prepared as described in Method 1 below; 300 mg, 0.76 mmol) in dichloromethane (7 ml) and N,N-dimethylformamide (0.5 ml). tert-Butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate may also be prepared according to the process described in Method 4 below. Acetic acid (50 μl, 0.87 mmol) was added and the reaction mixture allowed to stir at ambient temperature for 45 minutes. Sodium triacetoxyborohydride (250 mg, 1.18 mmol) was then added and reactions allowed to stir for a further 76 hours, before being diluted with methanol and poured directly onto an SCX-2 cartridge (10 g). The cartridge was washed through with methanol (80 ml) before eluting the products with a 2M solution of ammonia in methanol (50 ml). The relevant fractions were evaporated to dryness and the resultant residue redissolved in dichloromethane (3 ml) and treated with trifluoroacetic acid (1 ml). This mixture was stirred at ambient temperature for 2 hours before diluting with dichloromethane and pouring onto an SCX-2 cartridge (5 g). The cartridge was washed with methanol (20 ml) then products eluted with a 2M solution of ammonia in methanol (20 ml). The ammoniacal fraction was evaporated to dryness and the resultant residue was purified by flash chromatography on silica, eluting with 10% methanol in dichloromethane, to afford the title compound (117 mg, 40%); NMR Spectrum: (DMSO d6) δ 1.70 (m, 4H), 2.01 (t, 2H), 2.57 (m, 1H), 2.95 (m, 2H), 3.38 (s, 2H), 3.81 (s, 3H), 4.86 (s, 2H), 6.60 (m, 1H), 6.78 (m, 1H), 6.97 (m, 1H), 7.18 (m, 1H), 7.31 (s, 1H), 7.37 (d, 2H), 7.57 (s, 1H), 7.91 (d, 2H), 9.56 (s, 1H); Mass Spectrum: M+H+390.

Provenance & Evidence