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US 10,836,781 B2Granted
Process for the preparation of tetrofosmin or acid salt thereof
AssigneeJubilant Generics Limited
InventorsMokkapati Umamaheshwar Prasad, Anjul Kumar, Shishupal Singh, Dharam Vir
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Abstract
The present invention relates to an improved process for the preparation of tetrofosmin or acid addition salt thereof. The present invention also relates to the process for the preparation of tetrofosmin disulfosalicylate salt. Further the present invention also provides the polymorphic form J of disulfosalicylate salt of tetrofosmin.
Claims13
A process for the preparation of tetrofosmin or acid salt thereof, comprising:
- a) reducing diethylbenzylphosphonate of Formula 8
- by treating with a suitable reducing agent in the presence of a suitable solvent, optionally in the presence of catalyst, to provide benzyl phosphine of Formula 9;
- b) coupling the benzyl phosphine of Formula 9 with vinyl ethyl ether of Formula 3
- using a catalyst, optionally in the presence of a suitable solvent to provide benzylbis(2-ethoxyethyl)phosphane of Formula 4, with the proviso that said coupling step is not carried out under photolytic conditions;
- c) coupling of benzylbis(2-ethoxyethyl)phosphane of Formula 4 with 1,2-dibromoethane of Formula 10,
- optionally using a suitable solvent, to provide ethane-1,2-diylbis(benzylbis(2-ethoxyethyl)phosphonium)bromide of Formula 11;
- d) converting the ethane-1,2-diylbis(benzylbis(2-ethoxyethyl) phosphonium) bromide of Formula 11 using a suitable base in the presence of suitable solvent into ethane-1, 2-diylbis(bis(2-ethoxyethyl)phosphine oxide of Formula 12;
- e) deoxygenating ethane-1, 2-diylbis(bis(2-ethoxyethyl)phosphine oxide of Formula 12 using the suitable reagent in the presence of suitable solvent to obtain tetrofosmin;
- and
- f) optionally, converting tetrofosmin into an acid salt thereof.
7 more elements
Dependencies are inferred from the claim text.