The synthesis of thyrotropin releasing hormone (TRH) analogues is described as follows: The reduction of N-benzyloxycarbonylprolinamide (I) with H2 over Pd/C in methanol gives prolinamide (II), which is condensed with N-benzyloxy-carbonylhistidyl hydrazide (III) by means of NaNO2 - HCl in ethyl acetate yielding N-benzyloxycarbonylhistidylprolinamide (IV). The hydrolysis of (IV) with HBr in acetic acid affords histidylprolinamide (V), which is finally condensed with 6-methyl-5-oxothiomorpholinyl-3-carboxylic acid (VI) by means of 1-hydroxybenzotriazole, dicyclohexylcarbodiimide and triethylamine in DMF.

The synthesis of thyrotropin releasing hormone (TRH) analogues is described as follows: The reduction of N-benzyloxycarbonylprolinamide (I) with H2 over Pd/C in methanol gives prolinamide (II), which is condensed with N-benzyloxy-carbonylhistidyl hydrazide (III) by means of NaNO2 - HCl in ethyl acetate yielding N-benzyloxycarbonylhistidylprolinamide (IV). The hydrolysis of (IV) with HBr in acetic acid affords histidylprolinamide (V), which is finally condensed with 6-methyl-5-oxothiomorpholinyl-3-carboxylic acid (VI) by means of 1-hydroxybenzotriazole, dicyclohexylcarbodiimide and triethylamine in DMF.

The synthesis of thyrotropin releasing hormone (TRH) analogues is described as follows: The reduction of N-benzyloxycarbonylprolinamide (I) with H2 over Pd/C in methanol gives prolinamide (II), which is condensed with N-benzyloxy-carbonylhistidyl hydrazide (III) by means of NaNO2 - HCl in ethyl acetate yielding N-benzyloxycarbonylhistidylprolinamide (IV). The hydrolysis of (IV) with HBr in acetic acid affords histidylprolinamide (V), which is finally condensed with 6-methyl-5-oxothiomorpholinyl-3-carboxylic acid (VI) by means of 1-hydroxybenzotriazole, dicyclohexylcarbodiimide and triethylamine in DMF.