Amino production

Amino-dehydrogenation (SnH) using the LA/PP system was also studied with the 3,6-dinitro-l,8-naphthyridines (87a-87d) (86JHC473 93LA471). Besides mono amino products, diamino products are also obtained the yields are, however, moderate. 

The reaction of 2-bromo-5-nitrothiazole with weakly basic secondary aliphatic amines gave the expected 2-amino products. The isomeric 5-bromo-2-nitrothiazole with such amines gave mixtures of the expected 5-amino products along with 2-aminated 5-nitrothiazole rearrangement products. A mechanism was proposed which involves the slow thermal isomerisation of the 5-bromo-2-nitrothiazole to the much more reactive 2-bromo isomer which competes, in the case of relatively weak amine nucleophiles, with direct but slow displacement of the 5-bromo group to form the normal displacement product <96JHC1191>. 

Whereas silylation-amination of 2-amino-5,8-dihydroxypyrimido[4,5-d]pyridazine 269 with 3-amino-l-propanol, HMDS 2, and TsOH affords, after 24 h at 120-140 °C, the mono-8-hydroxypropylamino derivative 270 in 50% yield [79], reaction of 269 with a shght excess of ethanolamine and HMDS 2 provides, after 30 h at 120-150°C, only 20% of the bis(amino) product 271 [79]. (Scheme 4.31) A larger excess of ethanolamine and longer reaction times wiU certainly increase the yield of 271. 

To ascertain that aminomethylphosphonic acid ( ) but not glycine (4) is a photolysis product, the primary amino product was identified by comparison of TLC Rf values. Possible products and their formation pathways from photolytic cleavage of N-nitrosoglyphosate are shown in Figure 1 (5). The TLC Rf values on silica gel for different solvent systems are shown in Table II (5). The data clearly indicate that aminomethylphosphonic acid... 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

The conjugate addition of activated nitrogen nucleophiles, such as hydroxylamine and hydrazine derivatives, to a,/3-unsaturated bicyclic lactam 284 gave the corresponding /3-amino product 285 in good yield and excellent diastereoselectivity. These products can be manipulated to afford enantiopure /3-aminopyrrolidinones of potential application as conformationally constrained, substituted glutamate templates (Equation 45) <2001J(P1)2997>. 

The amino-debromination of 6-bromo-4-phenylpyrimidine (Scheme 1.3). The reaction has been proved to occur by the formation of an initial ct-adduct at C-2, which subsequently rearranges into the 6-amino product [Sn(ANRORC) mechanism]. 

When amination-without-quenching is carried out with N-labeled potassium amide/liquid ammonia and the degree and position of labeling in both amino products are determined, it appears that the incorporation of the label in the pyrimidine ring of 2-amino-4-phenylpyrimidine 61 has decreased from 92 to 52% see Table II.8. Thus, not only the yield of the 2-amino product is lower, but also the fraction that is formed via a ring opening-ring closure sequence [Sn(ANRORC) mechanism]. 

Finally, a one-pot, three-component condensation reaction in water provides an efficient procedure for the synthesis of furo[2,3-r/ pyrimidine-2,4(1/7,3//)-diones 303 (Scheme 26). A, A -Dimethylbarbituric acid 301 and 4-nitrobenzaldehyde 302 are reacted with a series of isocyanides to give good yields of the 6-amino products 303 <2002TL9151, 2005SC535>. 

Quaternary salts having structure 51 have been isolated R, and R2 are amino, alkoxy, and thioalkoxy substituents. Except in the case of 2-amino products, dealkylation to give a 2-pyrimidone takes place readily under alkaline conditions.158... 

Czuba07 prepared 2-, 3-, and 4-bromo-1,5-naphthyridine and treated them with potassium amide in liquid ammonia. The results of this study were explained by the intermediacy of 1,5-naphthyridyne-3,4 (133)149 in the reaction of the 3- and 4-bromo derivatives. A competing addition-elimination mechanism was also suggested since the ratios of the amino products from the 3- and 4-bromo compounds were not the same.147... 

An interesting case of an odd tele substitution has been found when aminating 2-X-l,8-naphthyridine (X = Cl, Br) with liquid ammonia containing potassium amide.10 29,30 The product obtained in the amination was 2-(or 7-) amino-1,8-naphthyridine (58). However, carrying out the amination with 2-X-7-deutero-l,8-naphthyridine (138), the 2-amino product had a deuterium content considerably less than was present in the starting material. From the amount of deuterium present in the 2-amino compound, it was calculated that for X = Br, 45% of the amino compound was formed according to the SN(AE) ele process and that for X = Cl, this percentage was considerably lower (10%).58... 

C10H14Oj) C,H. An alternate route leading from 2,3-xylenol to this diether via nitrogen-containing intermediates was explored. The sequence involved the reaction of 2,3-xylenol with nitrous acid (4-nitroso product, mp 184 °C dec.), reduction with sodium dithionite (4-amino product, mp about 175 °C), oxidation with nitric acid (benzoquinone, mp 5 8 °C), reduction with sodium dithionite (hydro-quinone) and final methylation with methyl iodide. The yields were inferior with this process. 

Italian company which was about to market generic Amikacin in Korea, they congratulated me, on the side, for our work on the Amikacin process. As soon as the Italian company s Amikacin appeared on the Korean market, we obtained samples and analyzed them. When the result came back showing that the Italian Amikacin contained the same profile of impurities as the Bristol-Myers product, and specifically that it contained no C-3-amino product, we were able to force the Italian product off the Korean market on the grounds of their infringement of the Bristol-Myers patent. 

Since the hydride is a very poor leaving group, the role of the oxidant is to provide, in a redox-type reaction, two electrons to convert this anionic adduct into a cationic species, which aromatizes into the amino product by proton elimination (Scheme 2). It cannot be excluded that under these conditions a one-electron process occurs, yielding a pyrimidyl radical, that aromatizes by loss of a hydrogen atom. 

Thus, 5-nitroquinoxaline on amination under the above-mentioned conditions gives substitution on position 2 (or 3). It is remarkable that no SnH substitution took place at the position 6, ortho to the nitro group, as was usually observed in the amination of the nitroquino-lines and nitronaphthyridines. Even when position 2 and 3 are occupied by a methyl group, no amination at position 6 was observed 2,3-dimethyl-5-nitroquinoxaline did not give any amino product (Scheme 22). 

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