Diethyl acetonedicarboxylate — a precursor for the synthesis of new substituted 4-aminoquinolines and fused 4-aminopyridines

Charvát, Tomáš; Potáček, Milan; Marek, Jaromı́r

doi:10.1007/bf00816102

Cited by 15 publications

(2 citation statements)

References 9 publications

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“…To remedy this problem, we investigated activated acetonedicarboxylate (ADC) derivatives, which had the added advantage of containing all the carbons required for the B-ring of naphthyridone (Scheme ). Treatment of ADC with 2,6-dichloroaniline and catalytic TsOH in refluxing toluene with azeotropic removal of water gave initially enamine diester 5 .…”

Section: Resultsmentioning

confidence: 99%

Efficient Synthesis of a Trisubstituted 1,6-Naphthyridone from Acetonedicarboxylate and Regioselective Suzuki Arylation

et al. 2005

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[reaction: see text] An efficient five-step synthesis of 1,6-naphthyridone 3b, a p38 mitogen-activated protein (MAP) kinase inhibitor intermediate, in 32% overall yield starting from acetonedicarboxylate (ADC) is described. The synthesis began with a selective monoamidation of ADC dimethyl ester enolate 9. A novel concomitant enamine formation and an imide cyclization afforded the nitrogen differentially protected enamide imide 12. Treatment of 12 with KO(t)Bu and 3-ethoxyacrylate produced lactam 15 quantitatively, which was converted to tetrachloronaphthyridone 19 via a one-pot p-methoxybenzyl (PMB) deprotection and bischlorination. A highly regioselective Pd(OAc)2/IMes-catalyzed Suzuki coupling completed the synthesis.

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Section: Resultsmentioning

confidence: 99%

Efficient Synthesis of a Trisubstituted 1,6-Naphthyridone from Acetonedicarboxylate and Regioselective Suzuki Arylation

et al. 2005

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“…Tin(IV) chloride has been shown to facilitate the carboncarbon bond formation between the cyano group of nitriles and active methylene compounds [6][7][8][9][10][11][12]. This reaction suggests the possibility that when 1a is treated with ethyl acetoacetate in the presence of tin(IV) chloride, the intermediate β-enaminoester B initially formed may undergo cyclization to furnish the expected 2a.…”

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confidence: 99%

Synthesis of 5,6‐dihydrothieno(and furo)pyrimidines bearing an active methine group at the 4‐position

Maruoka

Yamagata

Yamazaki

2001

Journal of Heterocyclic Chem

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The reactions of 2-benzamido-4,5-dihydro-3-thiophene(and -3-furan)carbonitriles (1a-c and 4a-c) with ethyl acetoacetate in the presence of tin(IV) chloride and triethylamine provided the corresponding ethyl 2-(5,6-dihydro-2-phenylthieno(and furo) [2,3-d]pyrimidin-4-yl)-3-oxobutanoates (2a-c and 9a-c). Similarly, compounds 1a-c and 4a-c reacted with dialkyl malonates to give the corresponding dialkyl(5,6-dihydro-2-phenylthieno(and furo) [2,3-d]pyrimidin-4-yl)propanedioates (5a-c, 6a-c, 10a-c and 11a-c). J. Heterocyclic Chem., 38, 269 (2001).In search of new methods [1][2][3][4] for synthesizing 5,6-dihydrothieno[2,3-d]pyrimidines from 2-amino-4,5-dihydro-3-thiophenecarbonitriles, we showed that 2-benzamido-4,5-dihydro-3-thiophenecarbonitrile (1a) [5] reacts with malononitrile in the presence of sodium hydride to give the malononitrile derivative [3]. This reaction probably occurs via addition of the cyano group of 1a to malononitrile to form the intermediate β-enaminonitrile A, which undergoes cyclization to give the malononitrile derivative. However, when 1a was treated with active methylene compounds lacking cyano group such as ethyl acetoacetate and diethyl malonate under the same conditions, no reaction occurred, and 1a was recovered unchanged. Hence, in order to overcome this limitation, we attempted to find the reaction conditions for the reaction of 1a with ethyl acetoacetate.Tin(IV) chloride has been shown to facilitate the carboncarbon bond formation between the cyano group of nitriles and active methylene compounds [6][7][8][9][10][11][12]. This reaction suggests the possibility that when 1a is treated with ethyl acetoacetate in the presence of tin(IV) chloride, the intermediate β-enaminoester B initially formed may undergo cyclization to furnish the expected 2a. Although the reaction of 1a with ethyl acetoacetate in the presence of tin(IV) chloride gave the 4-amino-2,3-dihydrothieno[2,3-b]-pyridine derivative 3 [13] in 44% yield, the desired 2a could not be isolated. Iimori and co-workers [7] reported that this carbon-carbon bond formation is successfully effected by using a combination of Lewis acid and tertiary amine. Therefore, we examined the reaction of 1a with ethyl acetoacetate in the presence of tin(IV) chloride and triethylamine, and found that the reaction proceeded smoothly to give 2a. The present paper deals with the reaction of 1a-c and 2-benzamido-4,5-dihydro-3-furancarbonitriles 4a-c [14] with active methylene compounds.When a mixture of 1a-c, ethyl acetoacetate (1.5 equivalents), triethylamine (1.5 equivalents) and tin(IV) chloride (3 equivalents) in 1,2-dichloroethane was refluxed, 2a-c were obtained in moderate yields. In a similar fashion, the reaction of 1a-c with diethyl and dimethyl malonates resulted in the formation of the corresponding malonic ester derivatives 5a-c and 6a-c in good yields. The 1 H nmr spectra of 2a and 2b in deuteriochloroform show two singlets at near δ 2.00 and δ 2.40 for acetyl groups, a singlet at near δ 4.80 for a methine and a singlet at near δ 13.20 for ...

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ChemInform Abstract: Diethyl Acetonedicarboxylate ‐ A Precursor for the Synthesis of New Substituted 4‐Aminoquinolines and Fused 4‐Aminopyridines.

1995

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Diethyl acetonedicarboxylate — a precursor for the synthesis of new substituted 4-aminoquinolines and fused 4-aminopyridines

Cited by 15 publications

References 9 publications

Efficient Synthesis of a Trisubstituted 1,6-Naphthyridone from Acetonedicarboxylate and Regioselective Suzuki Arylation

Efficient Synthesis of a Trisubstituted 1,6-Naphthyridone from Acetonedicarboxylate and Regioselective Suzuki Arylation

Synthesis of 5,6‐dihydrothieno(and furo)pyrimidines bearing an active methine group at the 4‐position

ChemInform Abstract: Diethyl Acetonedicarboxylate ‐ A Precursor for the Synthesis of New Substituted 4‐Aminoquinolines and Fused 4‐Aminopyridines.

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