US EPA

7443035 

Journal Article 

2,3-DIHYDROSPIRO[1H-4-CYCLOHEXANE AND 5-AZABENZIMIDAZOLE-2,1'-CYCLOHEXANE] (=SPIRO[CYCLOHEXANE-1,2'(3'H)-1'H-IMIDAZO[4,5-B]PYRIDINE] AND SPIRO[CYCLOHEXANE-1,2'(3'H)-1'H-IMIDAZO[4,5-C]PYRIDINE]) - REACTIONS WITH NUCLEOPHILES 

Schwoch, S; Kramer, YWW; Neidlein, R; Suschitzky, H 

1994 

Yes 

Helvetica Chimica Acta
ISSN: 0018-019X 

77 

8 

2175-2190 

English 

10.1002/hlca.19940770811 

WOS:A1994PY60600010 

http://doi.wiley.com/10.1002/hlca.19940770811
Exit
 

The readily available title compounds 4a and 24 react with N‐, O‐, S‐, and C‐nucleophiles in presence of MnO2 to give the corresponding mono‐ or disubstituted 2H‐azabenzimidazoles ( = azaisobenzimidazoles), e.g., 11–18 and 26a–h, respectively, or 2,3‐dihydro‐1H‐azabenzimidazoles ( = dihydro‐azabenzimidazoles) such as 9 and 10 and 27 and 28, respectively, by a 1, 4‐ or 1,6‐Michael addition (Schemes 2 and 4). The bromo‐dihydro‐1H‐azabenzimidazole 4b lost the Br‐atom when treated with piperidine or morpholine yielding the corresponding disubstituted 2H‐azabenzimidazole 21 (Scheme 3). Reductive ring opening of the substituted spiro compounds leads to mono‐ and disubstituted diaminopyridines which are intermediates for fused pyridine ring systems with substituents often not available by conventional routes and of potential pharmaceutical interest (see 32–37). E.g., starting from 4a, a three‐step synthesis of the analgesic flupirtine maleate (= ethyl {2‐amino‐6‐[(4‐fluorobenzyl)amino]pyridin‐3‐yl}carbamate maleate = Katadolon®; 39) and of its non‐fluorinated derivative D‐7195 is described. Its analogue 40 was similarly made from the spiro compound 24. Copyright © 1994 Verlag GmbH & Co. KGaA, Weinheim 

analgesic agent; flupirtine; flupirtine maleate; pyridine derivative; article; drug structure; drug synthesis