Stannous Chloride → 5,6-Dichloropyridine-2,3-diamine

참여 물질

반응 단계

The compounds of the present invention may be prepared as follows. It has been reported that reduction of 2-amino-5-chloro-3-nitropyridine (2) by SnCl2 in concentrated HCl resulted in both reduction of the nitro group to an amino group as well as chlorination of the pyridine ring to give 2,3-diamino-5,6-dichloropyridine (4) as the only isolated product (Israel & Day, J. Org. Chem. 24:1455-1460 (1959)). We found that reduction of 2 under identical conditions as reported gave a mixture of 2,3-diamino-5-chloropyridine (3) and 2,3-diamino-5,6-dichloropyridine (4) in a ratio of 4:1. The mixture could not be separated by crystallization in water. It could be separated by preparative TLC and chromatography. Cyclization of 3 with oxalic acid gave 8-NQX 5 and cyclization of 4 with oxalic acid gave 8-NQX 6. 6,7-dichloro-8-NQX 6 was found to have a Ki of about 200 nM, which is similar to the corresponding 6,7-dichloro-QX. 6-Chloro-8-NQX 5 also was found to be about as active as the corresponding 6-chloro-QX. 6-Bromo-7-methyl-8-NQX (8) was found to have a Ki of about 200 nM. 6-NQX 11 and 6,8-diN-QX 13 also were found to be about as active as QX. ##STR8##

출처 및 근거