- Preparation method of granisetron intermediate
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The invention discloses a preparation method of a granisetron intermediate. The preparation method comprises the following steps: step 1, carrying out a Mannich reaction on acetone dicarboxylic acid represented by a formula III to obtain pseudopelletierine represented by a formula IV; step 2, carrying out a reaction on the pseudopelletierine and hydroxylamine to prepare 3-pseudopelletierine oximerepresented by a formula V; and step 3, carrying out preparation by adopting one of the following schemes: (1) carrying out catalytic reduction on the 3-pseudopelletierine oxime through sodium bis(2-methoxyethoxy)aluminumhydride and Lewis acid to obtain a crude product of endo-3-amine-9-methyl-9-azabicyclo[3,3,1]nonane represented by a formula I, and directly using the crude product of endo-3-amine-9-methyl-9-azabicyclo[3,3,1]nonane to prepare granisetron, or purifying the crude product of endo-3-amine-9-methyl-9-azabicyclo[3,3,1]nonane for preparing granisetron; and (2) carrying out catalytichydrogenation reduction on the 3-pseudopelletierine oxime through Raney nickel to obtain a mixture of endo-3-amine-9-methyl-9-azabicyclo[3,3,1]nonane, purifying the mixture to obtain endo-3-amine-9-methyl-9-azabicyclo[3,3,1]nonane represented by the formula I, and using the endo-3-amine-9-methyl-9-azabicyclo[3,3,1]nonane used for preparing granisetron. The method has the advantages of mild reaction conditions, high reaction yield and low cost, and is suitable for industrial production.
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- Studies on azabicylo systems II: Synthesis and pharmacological evaluation of 3β-amino-9-methyl-9-azabicyclo [3.3.1] nonane analogs
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Aminoamides (15a-15h) and aryloxyamides (16a-16f) of 3β- chloracetamido-9-methyl-9-azabicyclo [3.3.1] nonane (14) were synthesized by treating (14) with different amines and phenols. The compounds so synthesized were evaluated for their CNS effect as well as on their effect on spasmogenic activity of acetyl choline, histamine and adrenaline.
- Kaur, Jaswinder,Razdan, Balkishen,Ram, Veerma,Pant, Geeta
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p. 269 - 274
(2013/09/24)
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