3-Amino-2-methylpyridine → HCID 136228365, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of methyl 3-chloro-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzoate (0.14 g, 0.34 mmol, Example #E.1) and 3-amino-2-methylpyridine (0.04 g, 0.37 mmol) in anhydrous THF (10 mL), was added lithium bis(trimethylsilyl)amide solution (1.3 mL, 1 M in THF, 1.3 mmol), at about −40° C. The resulting mixture was stirred for about 30 min, at about −40° C., and then quenched by the addition of water (10 mL) and ethyl acetate (130 mL). The layers were separated and the organic layer was washed with water (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, ethyl acetate/methanol 100:0 to 0:100) and preparative HPLC (Table 2, Method a) to afford 3-chloro-N-(2-methyl-3-pyridyl)-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydro-pyrazolo[3,4-e][1,4]thiazepin-4-yl]benzamide (0.0162 g, 0.03 mmol, 9%): LC-MS (Table 1, Method b) Rt=3.70 min, m/z 491 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) 2.56 (3H, s), 2.70-2.90 (2H, m), 3.26-3.35 (1H, m), 3.63-3.71 (1H, m) 3.60-4.00 (1H, br s) 3.84 (3H, s) 6.91 (1H, s) 7.09 (1H, ddd, J=1.2, 4.8, 7.9 Hz) 7.21 (1H, dd, J=4.8, 8.2 Hz) 7.44 (1H, d, J=8.0 Hz) 7.58-7.64 (3H, m) 7.80 (1H, d, J=8.0 Hz) 7.92 (1H, d, J=2.0 Hz) 8.28-8.34 (2H, m) 8.48-8.51 (1H, m).

Provenance & Evidence