2- ethoxycarbonyl amines

The ethoxycarbonyl derivative 11 is converted into derivatives 12 of 2-pyrimidone by the action of primary aliphatic amines.291 The products 12cyclize to the 5-aminopyrimido[4,5-/>][l,5]ben-zodiazepinones 13 on heating with ethanolic triethylamine.292... 

Aminopyridotriazinones 123 were obtained from guanidines 122 in hot hydrochloric acid-dioxane solution however, yields were moderate. The intermediates 122 could be obtained from the reaction of 2-aminopyridine 120 with ethoxycarbonyl isothiocyanate, followed by treatment of thioureas 121 with amines in the presence of HgCl2 (Scheme 12) <2002JHC1061>. 

R, 25) -2- [(ethoxycarbonyl) amino] -1 -phenyl-1 -propanol [Brdnsted acid promoted reduction of c/-amino ketone to erythro a-hydroxy amine], 124-125... 

In an example given in Scheme 51, tricyclic system 331 is generated by cyclocondensation between the ethoxycarbonyl group at C-5 of the triazole ring and the amino group of the substituent at N-l. The process that starts from catalytic reduction of the nitro group in derivative 329 does not stop at amine 330, but the subsequent spontaneous cyclocondensation leads directly to product 331 that is isolated in 60% yield <2002EJM565>. 

Ethyl 3-azido-l-methyl-177-indole-2-carboxylate 361 is prepared in 70% yield by diazotization of amine 360 followed by substitution of the created diazonium group with sodium azide. In cycloadditions with nitrile anions, azide 361 forms triazole intermediates 362. However, under the reaction conditions, cyclocondensation of the amino and ethoxycarbonyl groups in 362 results in formation of an additional ring. This domino process provides efficiently 4/7-indolo[2,3-i ]l,2,3-triazolo[l,5- ]pyrimidines 363 in 70-80% yield (Scheme 57) <2006TL2187>. 

Aminal reduction (NaBH3CN, 2 M HC1, EtOH) of the C-5-methoxycarbonyl pyrroloimidazole 52a or its enantiomer 52b resulted solely in lactamization to pyrrolopyrazines 53a and 53b, respectively the C-5-ethoxycarbonyl pyrroloimidazole 52c similarly cyclized to 53c (Equation 5) <1996TL1711, 1997TL1647>. 

N-Debenzylation oft-amines.1 The reagent converts N-benzyl tertiary amines into the corresponding (3-(trimethylsilyl)ethoxycarbonyl derivatives, which are cleaved by fluoride ion (8, 470-471) to sec-amines. 

FIGURE 2.15 Peptide-bond formation from l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquino-line-mediated reactions of A-alkoxycarbonylamino acids.46 The intermediate is the mixed anhydride that is slowly generated in the presence of the attacking nucleophile without a tertiary amine having been added. 

High yields of secondary amines are obtained when solutions of nitriles in acetic acid are hydrogenated at room temperature and pressure over a 5% rhodium-on-alumina catalyst (equation 4) hydroxy, ethoxycarbonyl and tosylamino substituents are not affected23. 

The simplicity of the two-phase modification of the Gabriel synthesis of primary amines, via the N-alkylation of potassium phthalimide, makes the procedure considerably more convenient than the traditional method, which normally requires the use of anhydrous dipolar aprolic solvents. The reaction can be conducted under solid liquid conditions using potassium hydroxide in toluene [25], or with preformed potassium phthalimide [26, 27] (cf ref. 28). As is normal for acylation reactions, relatively mild conditions are required for the preparation of the A-ethoxycarbonyl derivative [29], whereas a reaction temperature of 100°C is generally used for N-alkylation (Table 5.16). The reaction time for the soliddiquid two-phase system can be reduced dramatically with retention of the high yields, when the reaction mixture is subjected to microwave irradiation [30]. 

The cycloalkylamine salts of 5-cyano-l-uracilacetic acid and analogues, exemplified by (LI), are claimed to produce marked inhibition of gastric secretion with virtually no anticholinergic activity [378]. This activity is not inherent in the free acetic acid nor in the amine. There is no distinction between optical isomers of the longer chain acids. The pyrimidine portion can be prepared by the treatment of a-cyano-/3-ethoxy-A -(ethoxycarbonyl)acrylamide with alanine or related derivatives [301,302]. 

Coupling the substituents to the polyacid core is a key step. The reaction must have a high yield to limit purification problems and show high selectivity between the amines and alcohols present to limit side reactions. The amidifica-tion reaction chosen is a coupling reaction used in peptide chemistry. The reaction is carried out at room temperature in the presence of a coupling reagent such as NjAT -dicyclohexylcarbodiimide, l-(3-dimethylaminopropyl)-3-ethylcar-bodiimide or l-ethoxycarbonyl-2-ethoxyl-l,2-dihydroquinoline, possibly in the presence of an activator such as hydroxybenzotriazole or N-hydroxysuccimide (Fig. 8). 

Tardella s group have developed effective protocols for preparation of chiral a-amino-carbonyl compounds using a-A-(ethoxycarbonyl) 0-(p-nitrobenzenesulfonyl)hydroxyl-amine 3n in the presence or absence of a base . A chiral /S-ketocarboxamide carrying... 

They also reported amination of chiral /3-enaminoesters derived from 2-ethoxycarbonyl-cyclohexanone (equation 19) and ethyl 2-butynoate (equation 20) using (/ )-l-phenyl ethylamine and chiral pyrrolidine, respectively. Amination was carried out without a base. 

Successful amination of chiral enamines and enol ethers by the same group took place using 3n in the presence of EtsN as a base. They obtained a-iV-(ethoxycarbonyl) aminoketones in low yields and stereoseletivities (Scheme 39). 

Chandrasekhar and colleagues used Af-acyl-Af, 0-bis(ethoxycarbonyl)hydroxylamines in a similar procedure to prepare amines. Aromatic Af-hydroxyimide derivatives were used by Marzoni and Varney " and Giitschow " to synthesize benz[crf]indol-2(l//)-one and 1-benzoxazin-4-one derivatives, respectively, via Lossen rearrangements. Both Af-benzyloxy and A-mesyloxy derivatives were used. 

The synthesis of 6-substituted derivatives 626 was achieved via reaction of 2-substituted-5-aminopyridine-4-car-boxylic acids and formamidine acetate in boiling 2-methoxyethanol <1996J(P1)2221>. The pyrido[3,4- lpyrimidinone 628 was prepared by amination of the thioureido derivative 627 with diisopropylamine followed by cyclization in boiling DMF <2004FRP2846657>. Pyridine 627 was prepared from the corresponding 3-amino derivative with ethoxycarbonyl isothiocyanate in DMF. 

Werden Thiokohlensaure-(ethoxycarbonyl-amide) nach obigen Bedingungen mit Hydroxyl-amin-Hydrochlorid und Natriumacetat in Ethanol umgesetzt, so erhalt man unter Ethanol-Abspaltung 5-Hydroxy-l, 2,4-oxadiazole182. 

Das durch Addition von 2-Isocyanat-tetrahydropyran an N-Hydroxy-carbamidsaure-ethyl-ester leicht zugangliche N-Ethoxycarbonyl-0-(2-tetrahydropyranylaminocarbonyl)-hydroxyl-amin cyclisiert im alkalischen Medium unter Ethanol-Austritt zu 3,5-Dihydroxy-1,2,4-oxa-diazol ... 

Die Hydrolyse zum Amin ist vielfach nur die letzte Stufe einer Reaktionsfolge und wird ohne Isolierung der Amid-Vorstufe durchgefuhrt, wie z. B. bei der Synthese von Diaryl-aminen ausgehend von 4,6-Diphenyl-2-ethoxycarbonyl-pyrylium-Salzen und Anilinen2. 

Sometimes the acetylenic ester rearranges to the corresponding allenic ester. For example, when the tnethyl amine salt of 3-chloro-2-ethoxycarbonyl -4-phenyl-2-hexenoic acid is refluxed in toluene, the allenic ester and acetylenic ester are obtained in a ratio of 3 7 (total yield 70%). There are alternative routes to cyclopropylpropiolic acids and esters, such as adding butyllithium to corresponding acetylenes and treating the product with carbon dioxide or methyl chloroformate. ... 

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