N,N-Dialkyl-β-hydroxyamides via the Reformatsky Reaction<sup>1,2</sup>

Drake, Nathan L.; Eaker, Charles M.; Shenk, W. J.

doi:10.1021/ja01182a073

Cited by 17 publications

(8 citation statements)

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“…N,N-Diethylbromoacetamide and 1-(bromoacetyl)piperidine, required for the preparation of 31b and 31c, respectively, were prepared fol- lowing the literature procedures. 8,9 Alkylation of quinazolin-4-ones has previously been reported to lead to N 3substituted products or a mixture of N 3 and O 4 products. 10 Only N 3 -substituted quinazolin-4-ones were observed in this study, as confirmed by 1 H NMR spectroscopy.…”

Section: Chemistrymentioning

confidence: 99%

“…First, the amino functionality (i.e., piperidin-1-yl) was introduced at the 2-position by a method analogous to that described for the N 3 -methylated derivatives; the N 3 substituent was then introduced by reacting 28 with the appropriate electrophile (e.g., methyl bromoacetate to prepare 29a ) in DMF using NaH as the base. N,N -Diethylbromoacetamide and 1-(bromoacetyl)piperidine, required for the preparation of 31b and 31c , respectively, were prepared following the literature procedures. , Alkylation of quinazolin-4-ones has previously been reported to lead to N 3 -substituted products or a mixture of N 3 and O 4 products . Only N 3 -substituted quinazolin-4-ones were observed in this study, as confirmed by 1 H NMR spectroscopy.…”

Section: Chemistrymentioning

confidence: 99%

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The Design and Synthesis of Water-Soluble Analogues of CB30865, a Quinazolin-4-one-Based Antitumor Agent

et al. 2002

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4-[N-[7-Bromo-2-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]-N-(3-pyridylmethyl)benzamide (CB30865) is a quinazolin-4-one antitumor agent whose high growth-inhibitory activity (W1L2 IC(50) = 2.8 +/- 0.50 nM) is believed to have a folate-independent locus of action. In addition, CB30865 represents a class of compounds with unique biochemical characteristics such as a delayed, non-phase specific, cell-cycle arrest. The low aqueous solubility of CB30865 prompted a search for more water-soluble analogues for in vivo evaluation of this class of compounds. It was thought that aqueous solubility could be increased by the introduction of amino functionalities at the 2-position of the quinazolin-4-one ring. A variety of compounds (5a-j, 31a-c, 32, and 33) were synthesized in a linear fashion starting from 3-chloro-4-methylaniline. Most of these compounds (e.g., 5a, 5b, 5g) were significantly more water-soluble than CB30865 (636 microM for 5a at pH 6 and 992 microM for 5g at pH 6). In addition, some of them were up to 6-fold more cytotoxic than CB30865 (e.g., for 5a, W1L2 IC(50) = 0.49 +/- 0.24 nM) and retained its novel biochemical characteristics.

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Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

The Design and Synthesis of Water-Soluble Analogues of CB30865, a Quinazolin-4-one-Based Antitumor Agent

et al. 2002

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“…21 The compounds EtCO-NH-CH(R)-COOCH, were synthesized from the reaction of C,H,COCl with glycine-or alanine-methyl ester. "…”

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confidence: 99%

Applications of ¹⁵N NMR spectroscopy to the study of unsymmetrically N‐substituted amides and model peptide compounds

et al. 1980

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C and '"N spectra of unsymmetrically N-substituted formamides and alkyl-, substituted alkyl-, and arylcarboxamides, which can be considered as model peptide compounds, were determined and discussed in terms of nitrogen lone pair delocalization. Differential solvent shifts and through-space steric effects are considered as a tentative explanation of the difference in screening between geomelrical diastereoisomers. 2-E assignment and the thermodynamic stability of diastereoisomers can also be predicted in somecircumstances from a consideration of the 15N chemical shifts. Data concerning small peptides are discussed in the light of the results obtained using the model compounds.

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“…The chloroacetic acid amides were prepared according to literature [13]. The phenacyl-bromides were purchased from Aldrich.…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, in the 13 C nmr the resonance corresponding to the methylsulfanyl group is at 13.16 ppm. The substitution pattern in the compound 12 was evidenced by 13 C nmr. According to a substitution in the 4 and 6 position of the pyrimidine the molecule is symmetric, however two different values for C4 and C6 were found.…”

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confidence: 99%

Synthesis and reactions of 6‐methylsulfanyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐carbonitrile

Briel

Franz

Dobner

2002

Journal of Heterocyclic Chem

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The synthesis of 6-methylsulfanyl-2,4-dithioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 4 is described. Compound 4 was reacted with various alkylants. The reaction with chloroacetic acid derivatives results in the formation of thieno[2,3-d]pyrimidines 8. When methyl iodide was used 2,4,6-tris(methylsulfanyl)pyrimidine-5-carbonitrile 5 was obtained. The substitution of the methylsulfanyl groups in compound 5 by several N-nuclophiles leads to amino substituted pyrimidines.

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N,N-Dialkyl-β-hydroxyamides via the Reformatsky Reaction^1,2

Cited by 17 publications

References 0 publications

The Design and Synthesis of Water-Soluble Analogues of CB30865, a Quinazolin-4-one-Based Antitumor Agent

The Design and Synthesis of Water-Soluble Analogues of CB30865, a Quinazolin-4-one-Based Antitumor Agent

Applications of ¹⁵N NMR spectroscopy to the study of unsymmetrically N‐substituted amides and model peptide compounds

Synthesis and reactions of 6‐methylsulfanyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐carbonitrile

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N,N-Dialkyl-β-hydroxyamides via the Reformatsky Reaction1,2

Cited by 17 publications

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The Design and Synthesis of Water-Soluble Analogues of CB30865, a Quinazolin-4-one-Based Antitumor Agent

The Design and Synthesis of Water-Soluble Analogues of CB30865, a Quinazolin-4-one-Based Antitumor Agent

Applications of 15N NMR spectroscopy to the study of unsymmetrically N‐substituted amides and model peptide compounds

Synthesis and reactions of 6‐methylsulfanyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐carbonitrile

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N,N-Dialkyl-β-hydroxyamides via the Reformatsky Reaction^1,2

Applications of ¹⁵N NMR spectroscopy to the study of unsymmetrically N‐substituted amides and model peptide compounds