2-Amino-1 -methyl-6-imidazo pyridine

Reaction of 2 equiv of 2-aminopyridines with 2-hydropolyfluoroalk-2-anoates 351 in MeCN in the presence of NEts at 90 °C for 50 h afforded a mixture of the isomeric 2-oxo-2H- and 4-oxo-4//-pyrido[l,2-n]pyrimidines 110 and 111. Reaction of 3 equiv of 2-amino-pyridines and 2-hydropoly-fluoroalk-2-enoates 351 in MeCN in the presence K2CO3 could be accelerated by ultrasonic irradiation (125W). 2-Amino-6-methylpyridine yielded only 2-substituted 6-methyl-4//-pyrido[l,2-n]pyrimidin-4-ones 111 (R = 6-Me), whereas 2-amino-5-bromopyridine gave a mixture of 7-bromo-4//-pyrido[l,2-n]pyrimidin-4-one (111, R = 7-Br, R = CF2C1) and 2-(chlor-o,difluoromethyl)-6-bromoimidazo[l, 2-n]pyrimidine-3-carboxylate in 44 and 8% yields, respectively (97JCS(P 1)981). Reactions in the presence of K2CO3 in MeCN at 90°C for 60h afforded only imidazo[l,2-n]pyrimidine-3-carboxylates. 

Z-aminO 1 -methy 1 6 phenylimidazo [4,5-b]-pyridine 2 aminO 3,7,8 trimethylimidazo[4,5 f]quinoxaline 2 aminO 3,4,7,8 tetramethyl 3H imidazO [4,5 f]quinoxaline inoxaline 3 aminO l,4 dimethyl SH pyrid [4,3 b] indole (Trp P I) and 3 aminO l methyl 5H pyrido [4,3 b]indole induced mutagenesis. Metabolic activation was required for positive results b... 

Trp-P-2 (3-amino-l-methyl-5//-pyrido[4,3-h]indole), AaC (2-amino-9//-pyrido[2,3-bJindole), MeAaC (2-amino-3-methyl-9//-pyrido[2,3- ]indole), and PhIP (2-amino-1-methyl-6-phenyl-imidazo[4,5-h]pyridine) and two /3-carbolines comutagens harman (l-methyl-9//-pyrido[4,3-h]indole) and norharman (9//-pyrido[4,3-h]indole). The optimized SPE procedure for isolation and preconcentration comprises the use of diatomaceous earth, propylsulfonyl silica gel, and C18 cartridges to separate selectively the imidazopyridine and indolpyridine derivatives from those of... 

Imidazo[4,5-b]pyridin-5(4H)-one, 3-amino-7-methyI-2-phenyl-methylation, 5, 616-617... 

Reactions with methylphenylcyclopropenone (154) provided an opportunity to compare the reactivities of the two different C—CO bonds. The reaction of 2-aminopyridines with methylphenylcyclopropenone (154) proceeded more slowly than with the diphenyl analog (153). In ether, formation of the ds-2-oxopyrido[l,2-a]pyrimidines (158 R1 = Me) and/or the imidazo[l,2-c<]pyridines (162) was observed, indicating that the cycloaddition proceeds via cleavage of the PhC—CO bond. The methyl-substituted trans-2-oxopyrido[l,2-a]pyrimidine (160 R1 = Me) was only detected in the reaction mixture of 2-amino-3-methylpyridine, where the H NMR spectrum exhibited signals assigned to 160 (R1 = Me, R = 9-Me). The compound was not isolated. The imidazo[l,2-a]pyridines (162) readily hydrolyzed to the acids (163), work-up therefore leading mainly to isolation of the acids. 

From 2-amino-6-methylpyridine only the imidazo [l,2-u]pyridine (162 R = 5-Me) was formed this was interpreted in terms of the steric effect of the 6-methyl group. 

A mixture of 3-(2-bromoethyl)-2-methyl-pyrido[l,2-a]pyrimidin-4-one monohydrobromide, 3-furan-2-yl-methyl-(3H-imidazo[4,5-b]pyridine-2yl)-4-piperidinyl)-amine dihydrobromide, of sodium carbonate and of N,N-dimethylformamide was stirred and heated overnight at about 70°C. The reaction mixture was poured onto water. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (94 6 by volume), saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 3-(2-(4-((3-(2-furanylmethyl)-3H-imidazo[4,5-b]pyridin-2-yl)amino)-l-piperidinyl)ethyl)-2-methyl-4H-pyrido[l,2-a]pyrimidin-4-one melting point 202°C. 

SYNS IMIDAZO(4,5-B)PYRIDINE, 2-AMINO-1-METHYL-6-PHENYL- lH-IMIDAZO(4,5-B)PYRIDIN-2-... 

Reaction of imidazo[4,5-fc]pyridine (97), but not its 5-amino derivative, with perphthalic acid (49JA1885) or hydrogen peroxide in acetic acid (66UC403) gave the A( -oxide (98). Peracetic acid was used to prepare the A7 -oxides of 6-bromo-, 6-chloro, 6-bromo-5- and -7-methyl-, and 5,7-dimethyl-imidazo[4,5-fc]pyridine (98) (59JOC1455). The N-oxides can be catalytically reduced to (97) (80JHC17S7). 

Figure 14.10 Structures of four of the most abundant HAA in cooked food. PhIP is 2-amino-l-methyl-6-phenylimidazo[4,5-6]pyridine, AocC is 2-amino-9/f-pyrido[2,3-Z)]indole, MelQx is 2-amino-3,8-dimethylimidazo[4,5-/]quinoxaline, and IFP is 2-amino-l,6-dimethylfuro[3,2-e]imidazo[4,5-6]pyridine.

In the laboratory of J.S. Felton, the synthesis of 2-amino-1-methyl-6-phenyl-1/-/-imidazo[4,5- i]pyridine (PHIP), a mutagenic compound isolated from cooked beef, and its 3-methyl isomer have been accomplished. The synthesis of PHIP began with the commercially available 3-phenylpyridine, which was aminated at the 6-position with sodium amide in toluene by the Chichibabin reaction in 58% yield. 

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