Diana Becerra

Microwave-assisted synthesis of pyrimido[4,5-b][1,6]naphthyridin-4(3H)-ones with potential antitumor activity

The 6,7,8,9-tetrahydropyrimido[4,5-b][1,6]naphthyridin-4(3H,5H,10H)-ones 4,5a-g and their oxidized forms 6,7a-g were obtained from the catalyst-free reaction of 6-amino-2-methylthiopyrimidin-4(3H)-one 3 and (E)-3,5-bis(benzylidene)-1-alkyl-4-piperidones 1,2a-g under Microwave irradiation and their subsequent oxidation process with p-chloranil. Eighteen of the new compounds were evaluated in the US National Cancer Institute (NCI), where compound 4g presented a remarkable activity against 57 cancer cell lines, with the most important GI(50) values ranging from 1.48 to 9.92 μM from in vitro assays.

Efficient synthesis of 2-acylquinolines based on an aza-vinylogous Povarov reaction

The aza-vinylogous Povarov reaction between α-ketoimines and α,β-unsaturated dimethylhydrazones in the presence of indium trichloride affords 2-acyl-4-alkyl-4-dimethylhydrazonomethyl-1,2,3,4-tetrahydroquinolines with good cis/trans diastereoselectivities. These compounds were readily transformed into highly substituted 2-acylquinolines using a two-reaction sequence involving the oxidative generation of a C-4 nitrile group, followed by its elimination under thermal conditions. Alternatively, a one-pot protocol based on the reaction of hydrazones with magnesium monoperoxyphthalate hexahydrate in refluxing methanol afforded the target 2-acylquinolines in good to excellent yields. This methodology was also extended to the preparation of 2-arylquinolines.

Hydrogen-bonding patterns in 3-alkyl-3-hydroxyindolin-2-ones

The molecules of racemic 3-benzoylmethyl-3-hydroxyindolin-2-one, C(16)H(13)NO(3), (I), are linked by a combination of N-H...O and O-H...O hydrogen bonds into a chain of centrosymmetric edge-fused R(2)(2)(10) and R(4)(4)(12) rings. Five monosubstituted analogues of (I), namely racemic 3-hydroxy-3-[(4-methylbenzoyl)methyl]indolin-2-one, C(17)H(15)NO(3), (II), racemic 3-[(4-fluorobenzoyl)methyl]-3-hydroxyindolin-2-one, C(16)H(12)FNO(3), (III), racemic 3-[(4-chlorobenzoyl)methyl]-3-hydroxyindolin-2-one, C(16)H(12)ClNO(3), (IV), racemic 3-[(4-bromobenzoyl)methyl]-3-hydroxyindolin-2-one, C(16)H(12)BrNO(3), (V), and racemic 3-hydroxy-3-[(4-nitrobenzoyl)methyl]indolin-2-one, C(16)H(12)N(2)O(5), (VI), are isomorphous in space group P-1. In each of compounds (II)-(VI), a combination of N-H...O and O-H...O hydrogen bonds generates a chain of centrosymmetric edge-fused R(2)(2)(8) and R(2)(2)(10) rings, and these chains are linked into sheets by an aromatic pi-pi stacking interaction. No two of the structures of (II)-(VI) exhibit the same combination of weak hydrogen bonds of C-H...O and C-H...pi(arene) types. The molecules of racemic 3-hydroxy-3-(2-thienylcarbonylmethyl)indolin-2-one, C(14)H(11)NO(3)S, (VII), form hydrogen-bonded chains very similar to those in (II)-(VI), but here the sheet formation depends upon a weak pi-pi stacking interaction between thienyl rings. Comparisons are drawn between the crystal structures of compounds (I)-(VII) and those of some recently reported analogues having no aromatic group in the side chain.

Crystal structure of 2-fluoro-N-(1,3-thia-zol-2-yl)benzamide.

In the title compound, C10H7FN2OS, the mean plane of the central amide fragment (r.m.s. deviation = 0.048 Å) makes dihedral angles of 35.28 (8) and 10.14 (12)° with those of the fluorobenzene and thiazole rings, respectively. The thiazole S and amide O atoms lie to the same side of the molecule. In the crystal, pairs of N—H⋯N hydrogen bonds connect the molecules into inversion dimers with R 2 2(8) motifs, and weak C—H⋯O interactions connect the molecules into C(6) [001] chains. Together, the N—H⋯N and C—H⋯O hydrogen bonds generate (100) sheets.

3,3'-[(1RS,3SR)-2-oxocyclohexane-1,3-diyl]bis[(3RS,3'SR)-3-hydroxyindolin-2-one] dihydrate: organic layers of R2(2)(8), R2(2)(16) and R6(6)(40) rings linked by tetrameric water aggregates.

The organic component of the title compound, C22H20N2O5·2H2O, exhibits approximate but noncrystallographic mirror symmetry. The molecules of the organic component are linked by a combination of one O-H...O hydrogen bond and two N-H···O hydrogen bonds to form sheets containing R2(2)(8), R2(2)(16) and R6(6)(40) rings. These sheets are linked into a continuous three-dimensional framework structure by cyclic centrosymmetric R4(2)(8) water tetramers. Comparisons are made with some simpler analogues.

(9E)-9-benzylidene-3-methyl-2-methylsulfanyl-5-phenyl-5,6,7,8,9,10-hexahydropyrimido[4,5-b]quinolin-4(3H)-one: polarized molecules within hydrogen-bonded bilayers.

The molecules of the title compound, C(26)H(25)N(3)OS, which was prepared by means of an acid-catalysed cyclocondensation reaction between a 6-aminopyrimidinone and 2,6-dibenzylidenecyclohexanone, exhibit a polarized electronic structure, namely (9E)-9-benzylidene-3-methyl-2-methylsulfanyl-5-phenyl-3,5,6,7,8,9-hexahydropyrimido[4,5-b]quinolin-10-ium-4-olate, involving charge separation in the vinylogous amide portion. Four hydrogen bonds, two each of the C-H...O and C-H...pi(arene) types, link the molecules into bilayers comprising inversion-related pairs of sheets, each containing a single type of R(4)(3)(36) ring.

(9E)-9-Benzyl­idene-2-methyl­sulfanyl-5-phenyl-6,7,8,9-tetra­hydro­pyrim­ido[4,5-b]quinolin-4(3H)-one: a hydrogen-bonded R22(8) dimer

In the molecule of the title compound, C25H21N3OS, which was prepared by mild oxidation of the corresponding 5,6,7,8,9,10-hexahydro analogue, the fused carbocyclic ring adopts an envelope conformation. Pairs of molecules are linked into cyclic centrosymmetric dimers by pairs of inversion-related N-H···O hydrogen bonds.