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ChemicalBook CAS DataBase List Indapamide
26807-65-8

Indapamide synthesis

3synthesis methods
Indapamide, 4-chloro-N-(2-methyl-1-indolinyl)-3-sulfamoylbenzamide (21.3.33), is synthesized from 2-methylendoline, the nitrosation of which gives 2-methyl- 1-nitrosoindoline (21.3.31). Reducing this with lithium aluminum hydride leads to formation of 1-amino-2-methylendoline (21.3.32). Acylating this with 3-sulfonylamino-4-chlorbenzoic acid chloride leads to (21.3.33).

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Yield:26807-65-8 95.5%

Reaction Conditions:

Stage #1:2-methyl indoline with triethylamine;hydroxylamine-O-sulfonic acid at 10;
Stage #2:4-chloro-3-sulphamoylbenzoic acid with dicyclohexyl-carbodiimide at 15; for 6 h;Reagent/catalyst;

Steps:

1-4 Example 1
Add 50ml of hydroxylamine-O-sulfonic acid solvent to the reaction flask, add 17g of 2,3-dihydro-2-methyl-1H-indole, add 260ml of DMI solvent, and add 15ml of triethylamine dropwise with stirring, Cool the temperature to 10 °C, add 16g 4-chloro-3-sulfabenzoic acid, add 18ml N,N-dicyclohexylcarbodiimide, control the reaction temperature at 15 °C, the reaction time is 6 hours,After the reaction, the insoluble matter was filtered off, and isopropanol-water solvent was added for recrystallization to obtain indapamide product with a yield of 95.5%.

References:

Tianjin He Zhi Pharmaceutical Group Co., Ltd.;Cai Zhihe CN112142643, 2020, A Location in patent:Paragraph 0042-0049

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