DEHYDRO ARIPIPRAZOLE

Dehydroaripiprazole (OPC-14857) is an active metabolite of Aripiprazole. Aripiprazole is an antipsychotic agent and is metabolized by CYP3A4 and CYP2D6 forming mainly Dehydroaripiprazole. Dehydroaripiprazole has with antipsychotic activity equivalent to Aripiprazole[1][2][3].

General procedure: To a solution of dehydro-Aripiprazole (1.0 g, 2.24 mmol) in 2-methyltetrahydroffiran (25 mE) was added silver carbonate (0.864 g, 3.13 mmol) and iodomethyl octanoate (0.764 g, 2.68 mmol) at room temperature. The reaction was stirred for5 days. The reaction was quenched with H20 (30 mE) and filtered through celite. The reaction was extracted with ethyl acetate (3x20 mE), washed with 5% w/v sodium sulfite solution (15 mE), brine (20 mE), dried over MgSO4 and concentrated. The product was purified by column chromatography on silica eluting with 0-70% ethyl acetate in heptane to provide Compound 1206 (0.602 g) as a pale orange oil.?H-NMR (300 MHz, CDC13) oe 7.95 (1H, d), 7.60 (1H, d), 7.21 (1H, m), 7.14 (2H, m), 7.07 (1H, dd), 6.95 (1H, m), 6.79(1H, d), 6.24 (2H, s), 4.12 (2H, m), 3.09 (4H, m), 2.68 (4H, m), 2.54 (2H, m), 2.36 (2H, t), 1.90 (2H, m), 1.77 (2H, m), 1.61 (4H, m), 1.23 (6H, m), 0.83 (3H, t). [M+H]=602.2General procedure: To a solution of dehydro-Aripiprazole (1.0 g, 2.24 mmol) in 2-methyltetrahydroffiran (25 mE) was added silver carbonate (0.864 g, 3.13 mmol) and iodomethyl octanoate (0.764 g, 2.68 mmol) at room temperature. The reaction was stirred for5 days. The reaction was quenched with H20 (30 mE) and filtered through celite. The reaction was extracted with ethyl acetate (3x20 mE), washed with 5% w/v sodium sulfite solution (15 mE), brine (20 mE), dried over MgSO4 and concentrated. The product was purified by column chromatography on silica eluting with 0-70% ethyl acetate in heptane to provide Compound 1206 (0.602 g) as a pale orange oil.?H-NMR (300 MHz, CDC13) oe 7.95 (1H, d), 7.60 (1H, d), 7.21 (1H, m), 7.14 (2H, m), 7.07 (1H, dd), 6.95 (1H, m), 6.79(1H, d), 6.24 (2H, s), 4.12 (2H, m), 3.09 (4H, m), 2.68 (4H, m), 2.54 (2H, m), 2.36 (2H, t), 1.90 (2H, m), 1.77 (2H, m), 1.61 (4H, m), 1.23 (6H, m), 0.83 (3H, t). [M+H]=602.2To a solution of dehydro-Aripiprazole (1.0 g, 2.24 mmol) in 2-methyltetrahydroffiran (25 mE) was added silver carbonate (0.864 g, 3.13 mmol) and iodomethyl octanoate (0.764 g, 2.68 mmol) at room temperature. The reaction was stirred for5 days. The reaction was quenched with H20 (30 mE) and filtered through celite. The reaction was extracted with ethyl acetate (3x20 mE), washed with 5% w/v sodium sulfite solution (15 mE), brine (20 mE), dried over MgSO4 and concentrated. The product was purified by column chromatography on silica eluting with 0-70% ethyl acetate in heptane to provide Compound 1206 (0.602 g) as a pale orange oil.?H-NMR (300 MHz, CDC13) oe 7.95 (1H, d), 7.60 (1H, d), 7.21 (1H, m), 7.14 (2H, m), 7.07 (1H, dd), 6.95 (1H, m), 6.79(1H, d), 6.24 (2H, s), 4.12 (2H, m), 3.09 (4H, m), 2.68 (4H, m), 2.54 (2H, m), 2.36 (2H, t), 1.90 (2H, m), 1.77 (2H, m), 1.61 (4H, m), 1.23 (6H, m), 0.83 (3H, t). [M+H]=602.2To a solution of dehydro-Aripiprazole (1.5 g, 3.36 mmol)2-methyltetrahydroffiran (30 mE) was added silver carbonate (1.853 g, 6.72 mmol) and hexyl iodomethyl carbonate (2.021 g, 7.05 mmol) in 2-methyltetrahydrofuran (4 mE) at room temperature. The reaction was stirred for 4.5 days. The reaction was quenched with H20 (30 mE) and filtered through celite. The reaction was extracted with ethyl acetate (3x20 mE), washed with brine (20 mE), dried over MgSO4 and concentrated. The product was purified by column chromatography on silica eluting with 1:1 ethyl acetate to dichloromethane to 2% MeOR in 1:1 ethyl acetate to dichloromethane to provide Compound-1240 (1.08 g) as a yellow oil.?H-NMR (300 MHz, CDC13) oe 7.96 (1H, d), 7.60 (1H, d), 7.21 (1H, m), 7.14 (2H, m), 7.03 (1H, dd), 6.94 (1H, m), 6.81(1H, d), 6.26 (2H, s), 4.18 (2H, m), 4.12 (2H, t), 3.09 (4H, m), 2.68 (4H, m), 2.53 (2H, m), 1.91 (2H, m), 1.78 (2H, m), 1.63(2H, m), 1.28 (6H, m), 0.86 (3H, t). [M+H]=604.2To a mixture of To a solution of dibenzylcarbamoyl chloride (1.7 g, 6.7 mmol) in pyridine (15 mL) was added To a solution of

Molecular Weight:446.4
XLogP3:4.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:7
Exact Mass:445.1323824
Monoisotopic Mass:445.1323824
Topological Polar Surface Area:44.8
Heavy Atom Count:30
Complexity:597
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes