ChemicalBook CAS DataBase List Palonosetron

Palonosetron synthesis

7synthesis methods

Product Name:Palonosetron
CAS Number:135729-56-5
Molecular formula:C19H22N2O
Molecular Weight:294.39

135729-78-1 Synthesis

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-5,6,7,8-tetrahydro-1-naphthalenecarboxamide

135729-78-1
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135729-56-5
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Yield: 95%

Reaction Conditions:

with sodium hydroxide;n-butyllithium in tetrahydrofuran;N-methyl-acetamide;hexane

Steps:

7 (S)-2-(1-Azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro-1H-benz[de]isoquinolin-1-one
n is 2; each p, q and u is 0; and R³ is 1-azabicyclo[2.2.2]oct-3-yl. A solution of n-butyllithium in hexane (60 mmol) was added dropwise at -70° C. to a solution of (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-5,6,7,8-tetrahydro1-naphthalenecarboxamide (7.70 g, 21 mmol), prepared as in Example 3, in dry tetrahydrofuran (400 mL). The reaction mixture was stirred at -10° C. for one hour, cooled to -70° C., and dimethylformamide (100 mmol) added in one portion. The reaction mixture was allowed to warm to room temperature over 1.5 hours, then cooled to 0° C. and acidified with 10% aqueous hydrochloric acid. The layers were separated, and the aqueous layer was washed with ethyl acetate, then made basic with 10N aqueous sodium hydroxide and extracted with ethyl acetate. The ethyl acetate was dried over anhydrous sodium sulfate, filtered, and evaporated to give 7.58 g (95% yield) of (S)-2-(1-azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro1H-benz[de]isoquinolin-1-one as white crystals; m.p. 117°-118° C.; [α]_D²⁵ +43.2° (c=0.98, CHCl₃). Crystallization from ethanolic hydrochloric acid gave 9.75 g of the hydrochloride salt monoethanol adduct as white crystals, m.p. >270° C., [α]_D²⁵ -8.4° (c=2.4, H₂ O). Anal.: Calcd. for C₁₉ H₂₂ N₂ O HCl C₂ H₅ OH: C, 66.91; H, 7.75; N, 7.43%. Found: C, 66.77; H, 7.65; N, 7.27%.