6-Amino-2-N-(n-propionylamino)selenazolo[4,5-f]indan의 합성

Synthesis of 6-amino-2-A^-(w-propionylamino)selenazolo[4,5-f]indan

2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. Selenium was reported to have an improved antioxidant ability and to reduce the loss of dopamine. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine agonist with low neurotoxocity. In order to develop a novel dopamine agonist, we tried to synthesize the selenazoloaminoindan derivative that is a hybrid structure of aminoindan and aminoselenazole instead of aminothiazole. 2-Indanone-2-oxime was reduced with TiCl4 and NaBH4 to form 2-aminoindan, which was reacted with propionyl chloride to give 2-N-n-propionylaminoindan (2). Compound 2 was reduced with TiCl4 and NaBH4 to afford 2-N-n-propylaminoindan (3) and it was nitrated and reduced to form 5-amino-2-N-n-propylaminoindan (5), which was reacted with KSeCN, Br2, and glacial acetic acid to give 4,6-dibromo-5-amino-2-N-n-propylaminoindan (7) instead of selenazole ring formation. Otherwise, compound 2 was nitrated and hydrogenated to form 5- amino-2-N-n-propionylaminoindan (9), which was treated with KSeCN, Br2, and glacial acetic acid to give 4,6-dibromo-5- amino-2-N-n-propionylaminoindan (10). Compound 9 was cyclized with KSeCN and glacial acetic acid in the absence of Br2 to give 6-amino-2-N-(n-propionylamino)selenazolo[4,5-f]indan (11).