Acetone → 2-[2-(Trifluoromethyl)-6-({4-[1-(trifluoromethyl)cyclopropyl]phenyl}sulfonyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]propan-2-ol

Participants

Reaction Conditions

Reaction Steps

To a solution of 8-iodo-2-(trifluoromethyl)-6-({4-[1-(trifluoromethyl)-cyclopropyl]phenyl}sulfonyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (intermediate 59, 150 mg, 0.235 mmol) in THF (1.5 mL) at 0° C. was added isopropylmagnesium bromide (1.89 mmol of a 2M solution in ether). After stirred at 0° C. for 40 min, acetone (204 mg, 3.52 mmol) was added dropwise and the reaction mixture was gradually brought to rt. The reaction was quenched with saturated aqueous NH4Cl and diluted with EtOAc. The organic layer was separated and the aqueous phase was extracted with EtOAc. The combined extracts were washed with water, brine, dried over MgSO4 and concentrated. Purification of the residue via SiO2 column chromatography provided the title compound. LC/MS: m/e 572.0 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.65 (1H, d, J=2.1 Hz), 7.56 (1H, d, J=7.5 Hz), 7.44 (1H, dd, J=8.5, 1.6 Hz), 7.21 (2H, d, J=8.3 Hz), 7.05 (1H, d, J=7.3 Hz), 7.02 (2H, d, J=8.5 Hz), 6.77 (1H, s), 6.74 (1H, J=8.2 Hz), 4.70-4.90 (2H, s, br), 1.64 (6H, s), 1.35-1.42 (4H, m), 1.26-1.30 (4H, m).

Provenance & Evidence