2-Aminopyridine hydrochloride

Exposure of 2-aminopyridine hydrochloride (Ca) and 2-amino-5-chloropyridine hydrochloride (Cb) to sunlight through Pyrex glass... 

The reaction of 2-aminopyridine hydrochlorides and allenic nitriles either neat at 90°C for 20 hours or in boiling methylene chloride for 15 hours afforded unstable 2-imino-2//-pyrido[l,2-a]pyrimidine hydrochlorides 71, which could be isolated as hydrates in about 50% yield [88JCS(P1)975]. If the reactions were carried out in boiling 95% ethanol for 72 hours, the initially formed 2-imino-2//-pyrido[ 1,2-a Ipyrimidines 71 were hydrolyzed and 2-pyridyl ketones 73 could be isolated. Under the latter conditions 3-hydroxy-2-aminopyridine gave 2-iminopyridopyrimidines 74, which were stabilized by the formation of zwitterionic structures (Scheme 5). [Earlier the ring-opened products 73 (R = H, 3-NH2) were described as a 4-imino-4/7-pyrido[ 1,2-a]pyrimidine derivative 72 (81TL4127)]. 

In the hydrogenation of 2-aminopyridine under acidic conditions two equivalents of hydrogen were absorbed, giving tetrahydroaminopyridine as the hydrochloride salt, which on further reduction was converted to piperidine hydrochloride and ammonia (74). When 2-aminopyridine hydrochloride was hydrogenated in aqueous solution four equivalents of hydrogen were absorbed, yielding piperidine hydrochloride and ammonia. 

A mixture of chloramine and ammonia with pyridine, 4-picoline, 2,4-lutidine, or nicotinic acid is reported to give the corresponding 2-amino derivative. 1-Aminopyridine hydrochloride as well as 2-aminopyridine hydrochloride are detected in aqueous solutions of chloramine and pyridine. ... 

Macartney et al. used CB[7] to mediate and template the stereoselective [4 + 4] photodimerization of 2-aminopyridine hydrochloride 36 [129]. In the presence of CB[7], 1 2 hosbguest inclusion complexes were formed, and photolysis gave exclusively the anti-trans addition photoproduct 37. In the absence of CB[7], both the anti-trans and the s)m-trans photoproduct are formed. Furthermore, they found that the formation of the photoproduct 37 inside the CB[7] nanoreactor stabilizes it significantly, preventing rearomatizalion back to the monomer reactants, which occurs thermally at room temperature in the absence of CB[7], This system is illustrated in Fig. 3.18. 

Wang R, Yuan L, Macartney DH. Cucurbit[7]uril mediates the stereoselective [4 + 4] photodeimerization of 2-aminopyridine hydrochloride in aqueous solution. J Org Chem 2006 71 1237-9. 

The other is the photo-dimerization of l-methyl-2-pyridoneii i to give (138). 2-Aminopyridine hydrochloride behaves similarlyi . 

Table 6.3 pH values for equimolal 4-aminopyridine/4-aminopyridine hydrochloride in 50% (w/w) methanol-water ... 

Infra-red spectra of solid aminopyridines and their solutions clearly indicate dimeric association in these compounds . Extensive data on the vibration spectra of aminopyridine hydrochlorides are available . 

Treating 5.5 g of 2-amino-4,5-dimethylthiazole HCl with 0.66 g of solid sodium hydroxide 15 min at 220°C yields 53% of 4.4. 5.5 -tetramethyT 2,2 -dithiazolylamine, whose structure w as proved by identification with the produa obtained from the reaction between dithiobiuret and 3-bromo-2-butanone (467). This result is comparable to the reaction between 2-aminopyridine and its hydrochloride to yield bis(pyridyl-2)amine (468). Gronowitz applied this reaction to 2-aminothiazole, refluxing it with its hydrochloride 4 hr in benzene and obtained the dimeric 2-aminothiazole (236). He proposed a mechanism (Scheme 143) that involves the addition of a proton to the 5-position of the ring to give 234. The carbocation formed then reacts on the 5-position of a second... 

Fluoropyridine. This isomer can be prepared in 54—81% yield by dia2oti2ation of 4-aminopyridine in anhydrous hydrogen fluoride (370,371,400). Eree 4-fluoropyridine readily undergoes self-quaterni2ation to give pyridyl pyridinium salts (401) stabili2ation can be effected as the hydrochloride salt (371,400). Numerous 4-fluoropyridinium salts, eg, 4-fluoro-l-methylpyridinium iodide, have been converted to novel penicillins (387,402). 

Ciclopirox may be produced as follows 2 g of 4-methyl-6-cyclohexyl-2-pyrone were heated with 1 g of hydroxylamine hydrochloride and 5 g of 2-aminopyridine to B0°C for B hours. 

This approach involves intermolecular cyclization of two six-membered heterocycles substituted with appropriate functional groups. Synthesis of 83 by the reaction between 2-aminopyridines and 3-ethoxycarbonyM-pipcridonc hydrochloride 82 in polyphosphoric acid is provided as an example (Equation 5) <1996T7789>. 

Reaction of carbon disulfide with primary amine hydrochloride in the presence of dimethyl aminopyridine (DMAP) and A,A -dicyclohexylcarbodii-mide (DCC) affords symmetrical thioureas (Scheme 44).124,125... 

By reacting 2-aminopyridine and epichlorohydrin, Knunjanz187 obtained the hydrochloride of 3-hydroxy-3,4-dihydro-2H-pyrido[l,2-a]pyrimidine (131 R = OH). Analogous products from 4-methyl-, 5-methyl-, 5-halo- and 3,5-dibromo-substituted 2-aminopyridines have been prepared by Soviet workers.188,189 The same products arose from the reaction of 2-aminopyridines and l,3-dichloro-2-propanol.188 189 Klusis and Kuthevicius190 reacted 2-aminopyridine with 3-chloro-1,2-propanediol (127) or 2,3-... 

Okamoto et al. prepared the pyrido[l,2-c<]pyrimidines (142 R = H, Me) by heating 2-aminopyridines with ethyl 3-chloropropionimidate hydrochloride in ethanol or acetonitrile. In the case of 2-aminopyridine and 2-amino-4-methylpyridine, not only 142 (R = H, 8-Me) but also the 2-imino derivatives were isolated, which on treatment with acid were transformed to 2-oxopyrido[l,2-c<] pyrimidines (142). With 2-amino-6-methylpyridine or... 

Later, it was also claimed that 3-(tetrazolyl)-4//-pyrido[ 1,2-u]pyrimidin-4-ones 159 were obtained in an one-step procedure by heating the appropriate 2-aminopyridine, ethyl (l//-tetrazol-5-yl)acetate, and triethyl orthoformate in dimethylformamide at 90°C for 1 hour, or in boiling tetra-hydrofuran for 6 hours followed by treatment with 1N potassium hydroxide at 50°C for 1 hour, or with anhydrous aluminum chloride under reflux for 6 hours (91EUP462834). 9-Methyl-3-( 1 //-tetrazolyl)-4//-pyrido[ 1,2-a]-pyrimidin-4-one 159 (R = 9-Me) could be prepared when 2-amino-3-meth-ylpyridine hydrochloride and sodium azide were suspended and stirred in dimethylformamide for 1 hour at room temperature, followed by the addition of ethyl ethoxymethylenecyanoacetate, ethoxymethylenemalo-nonitrile, ethyl cyanoacetate and triethyl orthoformate, or malononitrile and triethyl orthoformate and stirring at 90°C for 6-12 hours. Then the reaction mixture was treated with 1 N potassium hydroxide at 50°C for 1 hour, phosphoryl chloride at 90°C for 5 hours, or with concentrated hydrochloric acid at 110°C for 4 hours to give 26-62% yields. 

Refluxing ethyl 2-(3-aminopyridin-4-yl)hydrazinecarboxylate (419) in 36% methanolic hydrogen chloride for 8 hours gave l-aminoimidazo[4,5-c]pyridin-2(3i/)one hydrochloride (423), rather than the expected pyridotriazinone (420), thought to be an intermediate in the formation of (423) via (421) and (422) (76JHC601). 

Methoxy-5-nitropyridine (126) reacts readily with Af,/V-dimethyl-ethylenediamine in boiling water to give 89% of 127 (85EUP136730). Analogously, 4-ethoxy-3-nitropyridine-hydrochloride (128), is heated at reflux for 8.5 hr with an aqueous solution of ammonium acetate to afford 87% of 3-nitro-4-aminopyridine (129) (85EUP149537). 

In the preparation of 2-phenoxymethylperhydro-imidazo[l, 2-a]pyridine (221), the ring opening of 1,2-epoxy-3-phenoxypropane (219) with 2-aminopyridine followed by catalytic reduction of the hydrochloride of the resultant amino alcohol over Rh/C gave 220. Treatment of220 with thionyl chloride followed by base produced the required 221 (70IJC707). 

In PVA-coated capillaries it was possible to separate at pH 2.5 the standards of poly-2-vinylpyridinium hydrochloride (p(2-VPy)) in the molecular mass range between 1500 and 1,730,000 g mol-1 with dextran T70 as sieving matrix [20]. An example is shown in Fig. 4, where a 5% solution of dextran T70 has been used. The efficiency of the monomolecular basic marker 4-aminopyridine is excellent, demonstrating the exclusion of secondary adsorptive effects at the capillary surface. Hence, the broad peaks of the polymeric standards are due to their polydispersity. As in CE the width of the peaks depends on their migration velocity through the detection window, no direct comparison of broadness of the individual peaks and analyte polydispersity is possible. However, for each individual peak the methods applied in SEC for calculation of the different molecular mass averages can be applied. 

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