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US 9,802,934 B2Granted
Process for the synthesis of (R)-praziquantel
AssigneeTongli Biomedical Co., Ltd.
InventorMingxin Qian
Life of this patent
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Abstract
The present disclosure relates to a process and new intermediates for the synthesis of (R)-praziquantel, which is obtained through four steps in proper order, that is, condensation reaction, reduction reaction, acylation reaction and ring-closing reaction, using (1R)-2-substituted-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid as starting material. Overall, the present disclosure provides a (R)-praziquantel product with higher optical purity through a process route that is more cost effective and environmentally friendly.
Claims11
A process for the synthesis of (R)-praziquantel of formula 5:
- wherein the process comprises the following steps:
- 1) reacting a compound of formula 1:
- wherein R is selected from the group consisting of tert-butyloxycarbonyl, benzyloxycarbonyl, fluorenylmethoxycarbonyl, allyloxycarbonyl, trichloroethoxycarbonyl, p-methoxybenzyl and benzyl;
- with (a) chloroformate in the presence of a base and solvent, followed by ammonia, or (b) N,N′-carbonyldiimidazole in the presence of solvent, followed by ammonia, to provide a compound of formula 2:
- wherein R is selected from the group consisting of tert-butyloxycarbonyl, benzyloxycarbonyl, fluorenylmethoxycarbonyl, allyloxycarbonyl, trichloroethoxycarbonyl, p-methoxybenzyl and benzyl;
- 2) reacting the compound of formula 2 above with sodium borohydride in the presence of boron trifluoride diethyl etherate, to provide a compound of formula 3:
- wherein R is selected from the group consisting of tert-butyloxycarbonyl, benzyloxycarbonyl, fluorenylmethoxycarbonyl, allyloxycarbonyl, trichloroethoxycarbonyl, p-methoxybenzyl and benzyl;
- 3) reacting the compound of formula 3 above with cyclohexanoyl chloride in the presence of a base and solvent, followed by hydrochloric acid to provide a compound of formula 4:
- 4) reacting the compound of formula 4 above with chloroacetyl chloride in the presence of a base and solvent, followed by benzyltriethylammonium chloride, to provide (R)-praziquantel of formula 5:
6 more elements
Dependencies are inferred from the claim text.