Dimethylformamide → 2-[(1R)-8-[(4-[methyl[2-(pyridin-2-yl)ethyl]amino]cyclohexyl)oxy]-1H,2H,3H,4H-cyclopenta[alpha]inden-1-yl]acetamide

Participants

Reaction Conditions

Reaction Steps

The hydrochloride (111 mg, 0.29 mmol, 1.00 equiv) in 4 mL of distilled DMF was added DIEA (119 mg, 0.92 mmol, 3.13 equiv) and 2-(2-bromoethyl)pyridine (57 mg, 0.31 mmol, 1.04 equiv) at room temperature. The resulting solution was stirred overnight at 100° C. in an oil bath. The resulting mixture was diluted with water and extracted with DCM and concentrated under vacuum. The crude product (110 mg) was purified by preparative HPLC under the following conditions (Waters): column: Xbridge Prep C18, 5 um, 19*50 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 25% in 10 min, up to 95% in 1.5 min, down to 10% in 1.5 min); UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated under reduced pressure to remove CH3CN and water. The residue was lyophilized overnight to give the desired 2-[(1R)-8-[(4-[methyl[2-(pyridin-2-yl)ethyl]amino]cyclohexyl)oxy]-1H,2H,3H,4H-cyclopenta[α]inden-1-yl]acetamide (16.3 mg) as a light yellow solid. MS: m/z 466 (M+H)+. 1H NMR (400 MHz, CD3OD): δ 8.48 (d, 2H), 7.80 (t, 1H), 7.79 (d, 1H), 7.77-7.27 (m, 1H), 5.29-5.23 (m, 1H), 3.81-3.79 (m, 1H), 3.16-3.10 (m, 1H), 3.03-2.93 (m, 6H), 2.78-2.73 (m, 2H), 2.44 (s, 3H), 2.33-2.26 (m, 4H), 2.02 (d, 3H), 1.68-1.59 (m, 4H), 1.57-1.54 (m, 1H).

Provenance & Evidence