Ureas pyridyl

Factors influencing the choice of synthetic routes to pyrimidines depend very much upon the substitution pattern of the desired product. For pyrimidines unsubstituted at the 4- and 6-positions, a two-component ring synthesis reaction involving a 1,3-dialdehyde and a urea or amidine derivative is the most straightforward route, but only if the dialdehyde is readily available. For example, synthesis of 2-chloro-5-(2-pyridyl)pyrimidine 989, an intermediate in the synthesis of a selective PDE-V inhibitor, was achieved in two steps in 40% overall yield by condensation of 2-(2-pyridyl)malondialdehyde 987 with methylurea, followed by demethylation/chlorination of the pyrimidinone 988 with a mixture of POCI3 and PCls <20070PD237>. 

Simple side-chain reactions of 1,2-dithiin diols have been conducted. Besides the formation of esters, ethers (R = Me, Et, 7-Pr, cyclopropyl, Ph, pyridyl, cyclopentyl), and thioethers (R = H, TBDMS R = 4 -(4-hydroxyphenyl)-l//-tetrazole-5-thiol), selective oxidation of the primary alcohol groups in the presence of the 1,2-dithiin heterocycle could be readily achieved (Scheme 36) <1995JME2628, 1994SL201>. Additionally, amides, ureas, and carbamates of the dithiin diol were synthesized <1995JME2628>. 

Exciting motives obtained by hydrogen bonding of calixarenes bearing 2-pyridone [32b], carbonyl and pyridyl [32c], urea [32d], melamine and cyanuric acid [32e] and other acceptor and donor groups have been recently reviewed by Bohmerand Shivanyuk [32a]. 

Further derivatives of amines in which the a-C,H groups are sufficiently acidic to enable metalation are carbamates [235,238-240] (Scheme 5.26), imides[241], N-nitroso amines [59,242], ureas [201,243], some N-phosphorus derivatives [212, 214, 226, 244, 245], N-(2-pyridyl)amines (Scheme 5.26), and isonitriles [59]. A potential side reaction in the examples in Scheme 5.26 is the lithiation of the arene this is, in fact, observed with an isomeric dipyridopyrazine (last reaction, Scheme5.26). 

N-(2-methoxyphenyl)-N-(2(3-pyridyl)quinazolin-4-yl)urea ZM 241385 4-(2-[7-amino-2-(2-furyl)[l,2,4]triazolo[2,3-a][l,3,5]triazin-5-ylamino]ethyl)phenol. 

To the solution of 1.6 g of 4-aminopyridine in 7 ml of dimethylformamide 2.0 g of 2-chloroethylisocyanate are added while stirring and keeping the temperature below 40°C. After 2 h 28 ml of water are added and stirring is continued for 2 h at room temperature. The precipitate formed is filtered off, washed with water, dried to yield the l-(4-pyridyl)-3-(2-chloroethyl)urea, melting point 120°-122°C, (recrystallized from aqueous ethanol). 

To the suspension of 2.66 g of l-(4-pyridyl)-3-(2-chloroethyl)urea in 4 ml of boiling methanol, 2.68 g of 30.8% methanolic sodium methanolate are added while stirring and the mixture is refluxed for 1 h. It is filtered hot, washed with hot methanol, the filtrate evaporated, to yield the l-(4-pyridyl)-2-imidazolidinone, melting point 204°-207°C, (recrystallized from 90% aqeuous ethanol). 

Banerjee S, Adarsh NN, Dastidar P (2010) Selective separation of the sulfate anion by in situ crystallization of Cd-II coordination compounds derived from bis(pyridyl) ligands equipped with urea/amide hydrogen-bonding backbone. Eur J Inorg Chem 3770-3779... 

Bis(pyridyl)urea can bind as an A, (9-chelate with intramolecular hydrogen bonding toward various 3d M(II) transition metal ions (48), and as a tridentate anionic A,A, A"-chelate toward Co(III) (49) (109). The v(C=0) stretches in the complexes (1642-1672cm ) appear at lower frequency than in the free ligand (1700 cm ). 

As part of a study of host-guest complexation, the hydrogen-bonded dimerization of the substituted urea N-phenyl-N -(2-pyridyl)urea (U) in 1 1 CH2CI2/toluene was studied. The chemical shift of the high-field urea proton is especially sensitive to concentration (see Figure 22-20). 

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