Pyrimidine acylamino

Pyrimidine, 5-acetyI-2,4-dimethyI-synthesis, 3, 125 Pyrimidine, acylamino-deaeylation, 3, 85 Pyrimidine, alkoxy-hydrolysis, 3, 91 Primary Synthesis, 3, 134 synthesis, 3, 132, 134 Pyrimidine, 2-alkoxy-aminolysis, 3, 92 rearrangement, 3, 92, 135 synthesis, 3, 134 transalkoxylation, 3, 92 Pyrimidine, 4-alkoxy-aminolysis, 3, 92 rearrangement, 3, 92, 135 synthesis, 3, 134 transalkoxylation, 3, 92 Pyrimidine, 6-alkoxy-aminolysis, 3, 92 rearrangement, 3, 92, 135 synthesis, 3, 134 transalkoxylation, 3, 92 Pyrimidine, alkyl-halogenation, 3, 76 nitration, 3, 77 oxidation, 3, 76 synthesis, 3, 124... 

Shaw and McDowellhave prepared imidazolone derivatives by cyclization of a-acylamino amides. In a variation of this reaction the azlactone (30) was gradually converted to the hydroxamic acid (31) by methanolic hydroxylamine. Sodium methoxide and hydroxylamine readily gave the acyclic hydroxamic acid (32) which could be cyclized to 31 by dilute acid. Benzyloxyurea has been used in the sjrnthesis of pyrimidine hydroxamic acids (33) by reaction with /S-diketones followed by catalytic hydrogenation of the benzyl group. Protection... 

Partial saturation of the pyridazino ring of 3-acylamino-4//-pyrimido[l,2-A pyridazin-4-ones and the pyrazino ring of 3-acylamino-4//-pyrazino[l,2-tf]pyrimidin-4-ones in EtOH/AcOH system using Pd/C catalyst, resulted in the respective 6,7,8,9-tetrahydro derivatives in good yields <2000JHC783>. 

Unsaturated pyrazino[l,2-tf]pyrimidines were synthesized by formation of two bonds from [3+3] atom fragments. The 3-carbethoxy- and 3-acylamino-pyrazino[l,2-tf]pyrimidin-4-ones 81 and 87 were prepared from the 2-aminopyrazines 78 and 84 as depicted in Schemes 9 and 10, respectively. The mesoionic 95 was prepared as shown in Equation (8). 

Acylamino-2,4-dioxo-l,2,3,4-tetrahydro- bzw. 5-Acylamino-4-oxo-3,4-dihydro-pyrimidine werden durch Umsetzung mit ethanolischem Natriumhydroxid in Ausbeuten von 34-84% zu 4-Aminocarbonyl-5-methyl-imidazolen umgelagert437. 

Acylation of 95 with acid anhydrides or acid chlorides gives the acylamino-pyrazoles 97, which cyclize into pyrazolo[3,4-t/]pyrimidines upon treatment with alkaline or acidic media. Intermediates 98 or 99 have been proposed (56JA784 59JA2452). The acetylpyrazole 97 (R = R = H, R = CH3) is... 

The 5,6-double bond in activated pyrimidines such as 2-acylamino-6-acetyl-4(lH)-pyrimidinones (427) undergo Diels-Alder reactions to yield on heating with l-acetoxy-3-methylbutadiene (428) hydroquinazolines (429). The yields are modest, but the regiochemistry is clean. With 1,3-butadiene and with isoprene the cycloadducts were formed in low yields (83JOC3627). 

Cyclization of l-(acylamino)pyrimidine hydroiodides (1) with alkyl ammonium acetates gave 3//J5//-l,2,4-triazolo[l,5-a]pyrimidines (2) (87 EGP246999 89ZC378). Condensation of the l-(acylamino)pyrimidinium salt 3 with hydrazine hydrate gave 4, which upon cyclization with acetic acid in the presence of perchloric acid afforded the 3-amino-l,2,4-triazolo [l,5-a]pyrimidinium salt 5 (89EGP270711) (Scheme 2). 

The H mode of the pyrimidine ring construction assuming the stepwise formation of the N(l)-C(2) and C(2)-N(3) bonds as a result of the insertion of a component serving as the source of the C(2) atom is more often used in practice. The simplest modification involves intramolecular condensation of 3-(acylamino)thienopyri-dines produced by acylation of 3-amino-2-carbamoylthieno[2,3-Z>]pyridines or their structural analogs (1995PS83). An example is the synthesis of pyrimidothienobenzo-quinoline 98 from chloroacetamide 99. 

New 3/ -acylamino-nortropanes (19) with a variety of A—CO (aroyl, pyrimidine-carboxylic, etc.) and R (benzyl, heteroarylmethyl, etc.) groups have been synthesized as potential pharmaceutical agents.23... 

The 5,6-double bonds in activated pyrimidines such as 2-acylamino-6-acetyl-4(l//)-pyrimidinones 447 participate in DielsAlder reactions to yield, for example, hydroquinazolines 448 <1983JOC3627>. 

Appropriate precursors which have been used include 4-amino-5-nitroso-, 4-amino-5-nitro-and 4-amino-5-phenylazo-pyrimidines and 4-acylamino derivatives of these compounds. Various reducing agents and conditions have been used and these are described in Table 38. 

Higher acids or anhydrides give on heating the (acylamino)pyr midines, which may be cyclized to 8-alkylpurines. Thus, 8-butyladenine (2) is formed upon reaction with pentanoic anhydride via cyclization of the intermediate 5-(pentanoylamino)pyrimidine-4,6-diamine. ... 

Condensation of 3-acylamino-2-acylthiophenes 92 (R = COR) with ammonium formate gave the corresponding thienopyrimidines 93 (R, R = H or Me) [74CR(C)1513 76BSF151]. The substituted methyl derivatives of 93 (R = XCH2) were prepared by the action of nucleophilic reagents on l,2,3-triazolo[3,4-a]thieno[3,2-d]pyrimidines 94 (80JHC1771). 

A multistep preparation of a thieno[3,2-e]-l,4-diazepin-2(3//)-one (285) has been accomplished, starting from the thienooxazinone 284 obtained from methyl 3-acetylaminothiophene-3-carboxylate (283) and phosphorus pentachloride.154 Similarly, 3-methylthieno[2,3-d]pyrimidin-4-(3//)-ones (288) were obtained in an exothermic reaction by heating methyl 2-acylamino-3-thiophenecarboxylates (286) with N,AT-dimethylphosphordiamidate (287) up to 250°C155 (Scheme 78). Ethyl 2-acylamino-3-pyridinecarboxylate (289) gave, on heating with excess amine hydrochloride and phosphorus pentoxide/iV,AP-dimethylcyclohexylamine, a series of pyrido[2,3-d]pyrim-idine-4(3if)-ones (290).156... 

The synthesis of purines from monoacyl pyrimidine-4,5-diamines is a commonly used method (for example, [2252]). Similarly, 8-hydroxymethylpurin-6-one is synthesized from S-acylamino-6-aminopyrimidin-4-one and ethyl glycoiate but... 

An efficient cyclization of an aminonitrile under mild conditions (without external heat) is obtained by reacting it with chlorosulphonyl isocyanate (review [3340]) to give a high yield of pyrimidin-2-one [3368] heating with urea is also effective [2774]. The corresponding 4-one is formed in lower yield by heating an (acylamino)nitrile with a primary amine hydrochloride, a t-amine and phosphorus pentoxide [3789], or with acetic anhydride-pyridine [3898]. 

Prolonged heating of l,2,4-triazolo[4,3-c]pyrimidines (16) with water caused pyrimidine ring cleavage and afforded the 3-[l-(acylamino)-ethen-2-y 1 ]-1,2,4-triazoles 79. Compounds 79 are the acyclic intermediates... 

Cyclization of 2-(acylamino)pyridine-3-carbonitriles is catalyzed by strong acids such as hydrogen chloride or perchloric acid,16 and can be formulated as an intramolecular Ritter reaction17-22 (cf. Houben-Weyl, Vol.E5, pl032ff). Thus, after treatment with anhydrous hydrogen chloride in benzene solution, 2-(acylamino)nicotinonitriles give pyrido[2,3-if]-pyrimidin-4(l//)-ones 13.23... 

With alkaline hydrogen peroxide, the cyclization of 2-(acylamino)nicotinonitriles 14 yields pyrido[2,3-rf]pyrimidin-4(3//)-ones 15.24 This reaction apparently proceeds via the carbox-... 

Suitable cyclization partners are 2-(acylamino)nicotinic acids and primary amines, giving 2,3-disubstituted pyrido[2,3-r7]pyriinidin-4(3//)-ones. Thus, 3-aryl-2-methylpyrido[2,3-c/]pyrimidin-4(3/f)-ones 22 are synthesized by fusion of 2-acetamidonicotinic acid with arylamines.33... 

The reaction of ethyl 2-(acylamino)nicotinates with hydrochlorides of primary amines, phosphorus pentoxide and N,, V-di methy 1 cyc 1 ohexy 1 amine has been used to synthesize several substituted pyrido[2,3-c/]pyrimidin-4(3/7)-ones 24.36... 

The dimethylformamide/phosphoryl chloride reagent has been used to cyclize 6-(acylamino)-uracils by introducing the missing carbon unit.201 Thus, treating l,3-dimethyl-6-[(cyanoacetyl)amino]uracil with dimethylformamide/phosphoryl chloride yields 1,3-dimethyl-5-chloropyrido[2,3-rf]pyrimidine-2,4,7(l//,3f/,8//)-trione (8, R = H). 

If the pyrido[2,3-c/]pyrimidine system contains a suitable leaving group in the 4-position, addition of hydroxide anion at C2 will lead to the cleavage of the C2 — C3 bond, yielding a 2-(acylamino)nicotinonitrile, as in the reaction of pyrido[2,3-d]pyrimidine-4-thiol (3) with chloroacetic acid and sodium carbonate.364... 

The ring closure between a 2-carboxamide and a 3-(acylamino) function in the pyridine nucleus, effected by phosphoryl chloride424 or by refluxing with aqueous sodium hydroxide/ pyridine," yields the corresponding pyrido[3,2-c/]pyrimidin-4(3f/)-ones, e.g. 2. 

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