ChemicalBook CAS DataBase List DEHYDRO ARIPIPRAZOLE

DEHYDRO ARIPIPRAZOLE synthesis

3synthesis methods

Product Name:DEHYDRO ARIPIPRAZOLE
CAS Number:129722-25-4
Molecular formula:C23H25Cl2N3O2
Molecular Weight:446.37

129722-12-9 Synthesis

129722-12-9
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$5.00/100mg

129722-25-4
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$45.00/100mg

Yield:129722-25-4 92%

Reaction Conditions:

Stage #1:aripiprazole with trifluoroacetic acid;2,3-dicyano-5,6-dichloro-p-benzoquinone in tetrahydrofuran at 20; for 0.666667 h;Inert atmosphere;large scale reaction;
Stage #2: with sodium hydroxide in tetrahydrofuran;water; pH=12

Steps:

1
Example 1 Large scale synthesis of dehydroaripiprazole [7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)quinolin-2(1H)-one] (Compound 1; Formula VI) Aripiprazole (Formula VIA; 15 g, 0.03 mol) was dissolved in anhydrous tetrahydrofuran (360 mL). Trifluoroacetic acid (12 mL, 0.16 mol) was added to the clear solution. 1,2-Dichloro-4,5-dicyano quinone (24.3 g, 0.11 mol) was added and the mixture was stirred at room temperature under nitrogen atmosphere. The reaction was stirred for 40 minutes and TLC showed no starting material remaining Water (1.5 L) was added then reaction mixture basified with 50% aq NaOH until pH 12. The reaction mixture was extracted with dichloromethane (3*μL) and the combined organics were dried (MgSO₄) to give the crude product. This was purified by column chromatography on silica eluting with dichloromethane to 10% methanol/dichloromethane. The product was further purified by recrystallisation from 2-propanol to give the desired product (13.7 g, 92%) as an off white solid. ¹H-NMR (400 MHz, CDCl₃) δ 12.33 (1H, br s), 7.72 (1H, d), 7.42 (1H, d), 7.16-7.11 (2H, m), 6.98-6.93 (1H, dd), 6.83-6.79 (2H, m), 6.53 (1H, d), 4.10 (2H, t), 3.09 (4H, br s), 2.67 (4H, br s), 2.52 (2H, t), 1.93-1.70 (4H, m). LCMS (acidic method) [M+H]⁺ 446.02, rt 14.246 min.

References:

Alkermes, Inc. US2011/275803, 2011, A1 Location in patent:Page/Page column 60-61

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41202-77-1 Synthesis