Piretanide, Hoe-118, Eurelix, Tauliz, Arelix

4-Phenoxy-3-(1-pyrrolidinyl)-5-sulfamoylbenzoic acid; 3-(Aminosulfonyl)-4-phenoxy-5-(1-pyrrolidinyl)benzoic acid

55837-27-9

C17-H18-N2-O5-S

362.407

Aventis Pharma (Originator)

Diuretics, Loop Diuretics, RENAL-UROLOGIC DRUGS

Launched-1981

　

Drugs Fut

Piretanide

The esterification of 4-phenoxy-3-nitro-5-sulfamoylbenzoic acid (I) with methanol and H2SO4 gives the corresponding methyl ester (II), which is reduced with H2 over Raney-Ni in methanol yielding methyl 4-phenoxy-3-amino-5-sulfamoylbenzoate (III). The condensation of (III) with succinic anhydride (B) or succinoyl chloride (A) by means of pyridine in refluxing dioxane affords methyl 4-phenoxy-3N-succinimido-5-sulfamoylbenzoate (IV), which is reduced with borontrifluoride ethearate and NaBH4 in diglyme giving methyl 4-phenoxy-3-(1-pyrrolidinyl)-5-sulfamoylbenzoate (V). Finally, this compound is hydrolyzed with NaOH in water.

Hillier, K.; Casta馿r, J.

Hillier, K.; Casta馿r, J.; Piretanide. Drugs Fut 1977, 2, 6, 393

Drugs Fut1977,2,(6):393

Synthesis of Piretanide (EN:091078): The esterification of 4-phenoxy-3-nitro-5-sulfamoylbenzoic acid (I) with methanol and H2SO4 gives the corresponding methyl ester (II), which is reduced with H2 over Raney-Ni in methanol yielding methyl 4-phenoxy-3-amino-5-sulfamoylbenzoate (III). The condensation of (III) with succinic anhydride (B) or succinoyl chloride (A) by means of pyridine in refluxing dioxane affords methyl 4-phenoxy-3N-succinimido-5-sulfamoylbenzoate (IV), which is reduced with borontrifluoride ethearate and NaBH4 in diglyme giving methyl 4-phenoxy-3-(1-pyrrolidinyl)-5-sulfamoylbenzoate (V). Finally this compound is hydrolyzed with NaOH in water (1,2). (Scheme 09107801a) Description Crystals m.p. 225-7?(decomp). Manufacturer Hoechst AG (Germany). References 1. Merkel, W. et al.; Piretanide (Hoe 118) a new high ceiling salidiuretic; Eur J Med Chem 1976, 11(5), 399. 2. Bormann, D. et al. (Hoechst AG); DE 2419970.

Eur J Med Chem

Piretanide (Hoe 118) a new high ceiling salidiuretic

The esterification of 4-phenoxy-3-nitro-5-sulfamoylbenzoic acid (I) with methanol and H2SO4 gives the corresponding methyl ester (II), which is reduced with H2 over Raney-Ni in methanol yielding methyl 4-phenoxy-3-amino-5-sulfamoylbenzoate (III). The condensation of (III) with succinic anhydride (B) or succinoyl chloride (A) by means of pyridine in refluxing dioxane affords methyl 4-phenoxy-3N-succinimido-5-sulfamoylbenzoate (IV), which is reduced with borontrifluoride ethearate and NaBH4 in diglyme giving methyl 4-phenoxy-3-(1-pyrrolidinyl)-5-sulfamoylbenzoate (V). Finally, this compound is hydrolyzed with NaOH in water.

Merkel, W.; et al.

Merkel, W.; et al.; Piretanide (Hoe 118) a new high ceiling salidiuretic. Eur J Med Chem 1976, 11, 5, 399

Eur J Med Chem1976,11,(5):399

DE 2419970; FR 2324298; GB 1504505; US 4010273

5-Sulfamoylbenzoic acid derivatives carrying a heterocyclic substituent

The esterification of 4-phenoxy-3-nitro-5-sulfamoylbenzoic acid (I) with methanol and H2SO4 gives the corresponding methyl ester (II), which is reduced with H2 over Raney-Ni in methanol yielding methyl 4-phenoxy-3-amino-5-sulfamoylbenzoate (III). The condensation of (III) with succinic anhydride (B) or succinoyl chloride (A) by means of pyridine in refluxing dioxane affords methyl 4-phenoxy-3N-succinimido-5-sulfamoylbenzoate (IV), which is reduced with borontrifluoride ethearate and NaBH4 in diglyme giving methyl 4-phenoxy-3-(1-pyrrolidinyl)-5-sulfamoylbenzoate (V). Finally, this compound is hydrolyzed with NaOH in water.

Bormann, D.; et al.

Bormann, D.; et al.; 5-Sulfamoylbenzoic acid derivatives carrying a heterocyclic substituent. DE 2419970; FR 2324298; GB 1504505; US 4010273

DE 2419970; FR 2324298; GB 1504505; US 4010273,,():