Reaction #710596

Reaction equation

histamine dihydrochloride

1,5,7-dichloro-8-hydroxyquinoline-2-carboxylic acid

5,7-Dichloro-8-hydroxyquinoline-2-carboxylic acid

dicyclohexylcarbodiimide

1-hydroxybenzotriazole hydrate

→

5,7-Dichloro-8-hydroxyquinoline-2-carboxylic acid [2-(1H-imidazol-4-yl)-ethyl]-amide

Solvents

triethylamine

Conditions

Workup

1. 1
   Othergave
2. 2
   Otherafter column purification (silica gel, ethyl acetate/isopropanol/water (12:4:1)), 5,7-dichloro-8-hydroxyquinoline-2-carboxylic acid [2-(1H-imidazol-4-yl)-ethyl]-amide (PBT 1038) as a pale straw-coloured solid (276 mg, 34%)

Procedure

According to the procedure described in Example 1,5,7-dichloro-8-hydroxyquinoline-2-carboxylic acid 19 (597 mg, 2.31 mmol), dicyclohexylcarbodiimide (483 mg, 2.31 mmol), 1-hydroxybenzotriazole hydrate (316 mg, 2.31 mmol), histamine dihydrochloride (425 mg, 2.31 mmol) and triethylamine (0.5 mL) gave, after column purification (silica gel, ethyl acetate/isopropanol/water (12:4:1)), 5,7-dichloro-8-hydroxyquinoline-2-carboxylic acid [2-(1H-imidazol-4-yl)-ethyl]-amide (PBT 1038) as a pale straw-coloured solid (276 mg, 34%). 1H NMR (DMSO-d6, 400 MHz): δ 11.40 (br, 2H), 9.74 (m, 1H), 8.64 (d, J=8.6, 1H), 8.28 (d, J=8.6, 1H), 7.92 (s, 1H), 7.53 (s, 1H), 6.83 (s, 1H), 3.59 (m, 2H), 2.81 (m, 2H).

Source