Triphenylphosphine → HCID 136640165, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of rac-((4R,7S)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-yl)methanol (0.070 g, 0.16 mmol, Example #K.10) and triphenylphosphine (0.041 g, 0.16 mmol) in DCM (5 ml)/DMF (0.5 ml) at 0° C. was added 1-bromopyrrolidine-2,5-dione (0.028 g, 0.16 mmol). The reaction was stirred at 0° C. for about 2 h. The reaction was partitioned between DCM (25 mL) and saturated solution of NaHCO3 (40 mL). The organic layer was dried with Na2SO4, filtered and was concentrated in vacuo. The resulting residue was dissolved in DMF (1.5 ml) and cyanosodium (0.077 g, 1.57 mmol) was added. The reaction was heated at about 100° C. for about 1 h. The reaction was partitioned between EtOAc (25 mL) and brine (25 mL). The organic layer was washed with brine (25 mL), dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, 0-50% EtOAc/heptane) to give rac-2-((4R,7S)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-yl)acetonitrile (0.005 g, 0.005 mmol, 3%) as a white solid: LC-MS (Table 1, Method g): LC-MS (Table 1, Method g) Rt=2.57 min, m/z 454/456 (M+H)+; 1H-NMR (DMSO-d6, Bruker 400 MHz) δ 8.48-8.45 (m, 1H), 7.83-7.80 (m, 1H), 7.75-7.70 (m, 1H), 7.36 (d, J=2.0 Hz, 1H), 7.26-7.17 (m, 2H), 7.09 (d, J=8.3 Hz, 1H), 6.74 (s, 1H), 6.19 (d, J=5.7 Hz, 1H), 4.03-3.92 (m, 1H), 3.77 (s, 3H), 2.95-2.85 (m, 2H), 2.79-2.74 (m, 1H), 2.71-2.63 (m, 1H), 2.50 (s, 3H).

Provenance & Evidence