Regioselective lithiation of chiral 3-acylamino-2-alkylquinazolin-4(3H)ones: application in synthesis

Reaction of 3-amino-2-alkylquinazolin-4(3H)-ones with several chiral acid chlorides was found to be dependent on the molar proportions. When a 1:1 molar mixture was heated under reflux, the corresponding 3-(diacylamino)- derivatives were obtained in poor yields. However, when a 2:1 molar mixture was reacted in refluxing toluene, the 3-acylamino- derivatives were obtained in good yields based on the acid chloride. Lithiation of the 3-acylamino-2-alkyl­quinazolin-4(3H)-ones was achieved by the use of lithium diisopropylamide (LDA) in anhydrous THF at -78 °C and the reaction was regioselective at the carbon α to position 2 of the quinazolin-4(3H)-one moiety. The dilithio reagents thus obtained reacted with electrophiles to give the corresponding 2-substituted derivatives in very good yields. The NMR spectra of the products show the expected diastereotopism for all the CH2 groups and provide evidence for long-range asymmetric induction

Studies on Antiretroviral Drug Concentrations in Breast Milk: Validation of a Liquid Chromatography-Tandem Mass Spectrometric Method for the Determination of 7 Anti-Human Immunodeficiency Virus Medications

Studying the pharmacokinetics of antiretroviral drugs in breast milk has important implications for the health of both the mother and the infant, particularly in resource-poor countries. Breast milk is a highly complex biological matrix, yet it is necessary to develop and validate methods in this matrix, which simultaneously measure multiple analytes, as women may be taking any number of drug combinations to combat human immunodeficiency virus infection. Here, we report a novel extraction method coupled to high-performance liquid chromatography and tandem mass spectrometry for the accurate, precise, and specific measurement of 7 antiretroviral drugs currently prescribed to infected mothers. Using 200 µL of human breast milk, simultaneous quantification of lamivudine (3TC), stavudine (d4T), zidovudine (ZDV), nevirapine (NVP), nelfinavir (NFV), ritonavir, and lopinavir was validated over the range of 10–10,000 ng/mL. Intraday accuracy and precision for all analytes were 99.3% and 5.0 %, respectively. Interday accuracy and precision were 99.4 % and 7.8%, respectively. Cross-assay validation with UV detection was performed using clinical breast milk samples, and the results of the 2 assays were in good agreement (P = 0.0001, r = 0.97). Breast milk to plasma concentration ratios for the different antiretroviral drugs were determined as follows: 3TC = 2.96, d4T = 1.73, ZDV = 1.17, NVP = 0.82, and NFV = 0.21

Synthesis of glycosides containing quinazolin-4(3H)-one ring System

Reactions of various aminoquinazolin-4(3H)-ones with monosaccharides in the presence of a catalytic amount of glacial acetic acid afforded the corresponding N-glycosylamines as a mixture of b- and a-anomers. Acetylation of this mixture gave the corresponding b-glycoside acetates. However, b-glycoside acetates could be obtained directly from reactions of per-O-acetyl-b-D-glucosyl bromides with quinazolin-4(3H)-one derivatives which deacetyalted to the corresponding b-glycosides. A series of S-glycosides have been synthesised from reaction of per-O-acetyl-b-D-glucosyl bromides with quinazolinethiones

Synthesis of Novel 3H-Quinazolin-4-ones Containing Pyrazolinone, Pyrazole and Pyrimidinone Moieties

The diazonium salt of 3-(4-aminophenyl)-2-methyl-3H-quinazolin-4-one (2a) and its 6-bromo derivative 2b reacted with some active methylene compounds, namely ethyl acetoacetate (3), ethyl cyanoacetate (4) and acetylacetone (5), to afford the corresponding hydrazono quinazolinone derivatives 6-8. Treatment of 6a,b with hydrazine hydrate or phenyl hydrazine in refluxing ethanol afforded the corresponding pyrazolin-5-one derivatives of 3H-quinazolin-4-one 9a-d. Cyclization of 7a,b with hydrazine hydrate yielded the corresponding products 10a,b. Reaction of 8a,b with phenyl hydrazine or with urea afforded the corresponding derivatives 11a,b and 12a,b, respectively. Compounds 6-12 were identified by C,H,N analysis, IR, 1H-NMR, 13C-NMR and mass spectroscopy

Synthesis of Glycosides Containing Quinazolin-4(3H)-one Ring System

Reactions of various aminoquinazolin-4(3H)-ones with monosaccharides in the presence of a catalytic amount of glacial acetic acid afforded the corresponding N-glycosylamines as a mixture of b- and a-anomers. Acetylation of this mixture gave the corresponding b-glycoside acetates. However, b-glycoside acetates could be obtained directly from reactions of per-O-acetyl-b-D-glucosyl bromides with quinazolin-4(3H)-one derivatives which deacetyalted to the corresponding b-glycosides. A series of S-glycosides have been synthesised from reaction of per-O-acetyl-b-D-glucosyl bromides with quinazolinethiones

The Action of Methylmagnesioum Iodide on 6-Bromo-2-Phenyl-4H-3,l-Benzoxazinone and its 4(3H)-Quinazolinones

6-Bromo-2-phenyl-4H-3,l-benzoxazinone (7) reacted with methylmagnesium iodide to give 2-benzoylamino-5- bromophenyldimethylcarbinol (8) in 54% purified yield. Similarly, 3-anilino-6-bromo-2-phenyl-4(3H)-quinazolinone (9) afforded the corresponding dimethylcarbinol 10 in 65% yield after crystallization on its reaction with methylmagnesium iodide. However, reaction of methylmagnesium iodide with 6-bromo-3-(4-chloro-phenylidene)-2-phenyl- 4(3H)-quinazolinone (11) gave 6-bromo-3-[l-(4-chlorophenyl) ethylamino]-4(3H)-quinazolinone (12) in 48% yield after purification

A simple procedure for synthesis of 3H-quinazolin-4-one hydrazones under mild conditions

Condensation of 6-bromo- and 6,8-dibromo-2-hydrazino-3-phenyl-3H-quinazolin-4-ones with d-sugars in the presence of a catalytic quantity of glacial acetic acid gave the corresponding hydrazones in good yields. Acetylation of hydrazones with acetic anhydride in anhydrous pyridine gave the corresponding acetyl hydrazones in high yields. Also, other hydrazones were synthesized from condensation of 2-hydrazino-3H-quinazolin-4-ones with aromatic aldehydes in the presence of a catalytic quantity of piperidine

3-Arylazo-2-thioxo-2,3-dihydro-1H-quinazolin-4-ones as azodisperse dyes for dyeing polyester fabrics

Diazotized 3-amino-2-thioxo-2,3-dihydro-1H-quinazolin-4-one was coupled with various hydroxy aromatics to give the corresponding 3-arylazo-2-thioxo-2,3-dihydro-1H-quinazolin-4-ones in reasonable yields. The dyes produced were applied to polyester as disperse dyes and their fastness properties were elevated

ChemInform Abstract: Amadori Rearrangement of N-Glucosides of 6-Substituted 3-Amino-2-aryl- 4(3H)-quinazolinones.

Amadori rearrangement of N-glucosides of 6-substituted 3-amino-2-aryl-4(3H)-quinazolinones has been carried out by the condensation of equimolecular amounts of D-glucose and oxalate of 6-substituted 3-amino-2-aryl-4(3H)-quinazolinones (la-f) in boiling methanol. These compounds can also be obtained by heating the N-glucosides of 6-substituted 3-amino-2-aryl-4(3H)-quinazolinones (2a-f) in absolute methanol in the presence of dry oxalic acid. The products obtained are characterized by IR, 1H NMR, 13C NMR and mass spectral data and elemental analyses