22502-03-0

Basic information

• Product Name: 2-Methoxyethyl acetoacetate
• Synonyms: Methoxyethyl acetoacetat;2-METHOXYETHYL ACETOACETATE;ACETOACETIC ACID 2-METHOXYETHYL ESTER;ACMOE;2-METHOXYETHYL ACETOACETATE, WACKER QUAL ITY;Methoxyethylacetoacetate;ACETOACETIC ACID 2-(METACRYLOXY)ETHYL ESTER;2-Methyoxyethyl Acetoacetate
• CAS NO: 22502-03-0
• Molecular Formula: C₇H₁₂O₄
• Molecular Weight: 160.17
• EINECS: 245-043-8
• Product Categories: API intermediates;Diketene esters;Diketene Derivatives;Building Blocks;C6 to C7;Carbonyl Compounds;Chemical Synthesis;Esters;Organic Building Blocks
• Mol File: 22502-03-0.mol

Chemical Properties

• Boiling Point: 120 °C20 mm Hg(lit.)
• Flash Point: 218 °F
• Appearance: clear/
• Density: 1.09 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0721mmHg at 25°C
• Refractive Index: n20/D 1.434(lit.)
• Storage Temp.: 2-8°C
• PKA: 10.37±0.46(Predicted)
• Water Solubility: 100g/L at 20℃
• BRN: 2079850
• CAS DataBase Reference: 2-Methoxyethyl acetoacetate(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Methoxyethyl acetoacetate(22502-03-0)
• EPA Substance Registry System: 2-Methoxyethyl acetoacetate(22502-03-0)

Safety Data

• Hazard Codes: T,Xi
• Statements: 60-61-36/37/38
• Safety Statements: 53-26-45-24/25-37/39
• WGK Germany: 3
• Hazardous Substances Data: 22502-03-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-Methoxyethyl acetoacetate is used as an intermediate for the synthesis of pharmaceuticals, specifically in the production of Nimodipine, a medication used to prevent and treat certain conditions related to blood vessels in the brain.
Used in Organic Chemical Synthesis:
2-Methoxyethyl acetoacetate is also utilized as an intermediate in the synthesis of various organic chemicals, contributing to the development of a wide range of chemical products and applications.

InChI:InChI=1/C7H12O4/c1-6(8)5-7(9)11-4-3-10-2/h3-5H2,1-2H3

Upstream product

• 674-82-8 4-methyleneoxetan-2-one 
• 109-86-4 2-methoxy-ethanol 
• 141-97-9 ethyl acetoacetate 
• 85920-63-4 5-(1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 5394-63-8 2,2,6-trimethyl-4H-1,3-dioxin-4-one 

Downstream Products

• 124716-81-0 2-Methoxyethyl 2-<<(p-nitrophenyl)sulfonyl>oxy>acetoacetate 
• 145695-57-4 4-(3-Benzoyl-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid bis-(2-methoxy-ethyl) ester 
• 50899-10-0 methoxyethyl 3-amino-2-butenoate 
• 39562-22-6 (E/Z)-2-methoxyethyl 2-(3-nitrobenzylidene)-acetoacetate 
• 145695-56-3 4-(3-Benzoyl-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-(2-methoxy-ethyl) ester 
• 75130-29-9 J-6-163 
• 66085-59-4 nimodipin 
• 21881-78-7 3,5-diisopropyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate 
• 39562-75-9 3-ethyl 5-(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 
• 299452-61-2 2-methyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid (2-methoxyethyl) ester 
• 165390-06-7 bis(2-methoxyethyl) 4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate 
• 897627-86-0 bis(2-methoxyethyl) 4-(3-bromophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate 
• 897627-87-1 bis(2-methoxyethyl) 4-(4-bromophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate 
• 107610-58-2 2-Chloro-6-methyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 5-(2-methoxy-ethyl) ester 3-methyl ester 

Relevant articles and documents

Revisiting ageless antiques; synthesis, biological evaluation, docking simulation and mechanistic insights of 1,4-Dihydropyridines as anticancer agents

The historic DHP nucleus was serendipitously discovered by Arthur Hantzsch about 130 years ago and is still considered a hidden treasure for various pharmacological activities. Twenty-one DHP analogues were synthesized using the expedient one pot Hantzsch synthesis for screening as anticancer agents. Initially, the in vitro anti-proliferative single dose against a panel of 18 cancer cell lines showed that compounds 11b and 8f were the superlative candidates regarding their antitumor effect (GI% mean = 66.40% and 50.42%, correspondingly) compared to cisplatin (GI% mean = 65.58%) and doxorubicin (GI% mean = 74.56%). Remarkably, compound 11b showed a remarkable MDA-MB-468 anticancer activity (GI%=80.81%), higher than cisplatin (64.44%) and doxorubicin (76.72%), as well as strong antitumor activity against lung cancer A549 (GI%= 83.02%), more powerful than both cisplatin and doxorubicin. Compound 11b exhibited an exceptional anticancer activity against lung cancer cell line (A549) as its GI50 in nanomolar was (540 nM) with a 9-fold increase greater than cisplatin (GI50 = 4.93 μM) and with a selectivity index = 131 to cancer cells over normal cells. Further mechanistic investigations proved that DHPs anticipate simultaneously TOPI and RTKs (VEGFR-2, HER-2 and BTK) which can stimulate BAX/BAK and the executioner caspases via rtPCR studies.

Nimodipine impurity IV reference substance as well as preparation method and application thereof

The invention discloses a nimodipine impurity IV reference substance and a preparation method thereof. The method includes the steps that diketene, ethyl alcohol and triethylamine are taken and addedinto a container to be heated and cooled, reaction liquid is washed with water, washing liquid is discarded, anhydrous sodium sulfate is added and placed overnight, filtrate is obtained after filtration, ammonia gas is introduced into the filtrate until the filtrate is saturated, and the nimodipine impurity IV reference substance is obtained; and after the reaction is finished, m-nitrobenzaldehyde, methoxyethyl acetoacetate and ethanol are added, heating refulx is performed, the mixture is cooled and filtered, the solvent is removed through volatilization in a water bath to obtain a yellow viscous liquid, and recrystallization is carried out to obtain a yellow acicular crystal, namely the nimodipine impurity IV reference substance. The invention also discloses an application of the nimodipine impurity IV reference substance in nimodipine tablet consistency evaluation. According to the preparation method, the impurity IV can be prepared in a general analysis laboratory, special preparation equipment is not needed, the operation is simple, the purity of the obtained impurity reference substance can reach 98.4%, the purity requirement of the reference substance is met, and the preparation method can be used for consistency evaluation of the variety.

Design, synthesis, and molecular docking study of new monastrol analogues as kinesin spindle protein inhibitors

Lung, colorectal, and breast cancers are the top three types of cancer by incidence and are responsible for one-third of the cancer incidence and mortality. A series of 18 3,4-dihydropyrimidine analogues bearing a 1,2-methylenedioxybenzene component at position 4 with diverse side chains at positions 5 and 6 was designed and synthesized as inhibitors of the Eg5 kinesin enzyme. Target compounds were screened for their anticancer activity according to the NCI-USA protocol toward a panel of 60 cancer cell lines. Compounds 12a and 12b displayed the best antiproliferation activity against many cell lines. Interestingly, compound 12a displayed lethal effects against non-small-cell lung cancer NCI-H522 cells (?42.26%) and MDA-MB-468 breast cancer cells (?1.10%) at a single-dose assay concentration of 10?5 M. Compounds 11c, 11d, 11g, 12a–d, 13, 15, and 18a were assayed against the kinesin enzyme, with IC50 values ranging from 1.2 to 18.71 μM, which were more potent compared with monastrol (IC50 = 20 μM). Cell cycle analysis of NCI-H522 cells treated with compound 12a showed cell cycle arrest at the G2/M phase. Furthermore, the expression levels of active caspase-3 and -9 were measured. A molecular docking study was performed for some demonstrative compounds as well as monastrol docked into the allosteric binding site of the kinesin spindle protein.

Design, synthesis, and bioactivity of dihydropyrimidine derivatives as kinesin spindle protein inhibitors

A series of twenty-one 3,4-dihydropyrimidine derivatives bearing the heterocyclic 1,3-benzodioxole at position 4 in addition to different substituents at positions 2, 3 and 5 were designed and synthesized as monastrol analogs. The novel synthesized compounds were screened for their cytotoxic activity towards 60 cancer cell lines according to NCI (USA) protocol. Compounds 10b and 15 showed the best antitumor activity against most cell lines. Compound 15 was subsequently tested in 5-doses mode and displayed high selectivity towards CNS, prostate and leukemia subpanel with selectivity ratios of 22.30, 15.38 and 12.56, respectively at GI50 level. The IC50 of compounds 9d, 10b, 12, 15 and 16 against kinesin enzyme were 3.86 ± 0.12, 10.70 ± 0.35, 3.95 ± 0.12, 4.36 ± 0.14, and 14.07 ± 0.45 μM respectively, while the prototype compound, monastrol, reported IC50 value of 20 ± 0.42 μM. The safest compound among test compounds against normal cell line (HEK 293) is 10b with IC50 value of 62.02 ± 2.42 μM/ml in comparison to doxorubicin (IC50 = 11.34 ± 0.44 μM/ml). Cell cycle analysis of SNB-75 cells treated with compound 15 showed cell cycle arrest at G2/M phase. Further, the assay of levels of active caspase-3 and caspase-9 was investigated. Moreover, Molecular docking of compounds, 9d, 10b, 12, 15, 16, monastrol and mon-97 was performed to study the interaction between inhibitors and the kinesin spindle protein allosteric binding site.

NEW ANALOGS AS ANDROGEN RECEPTOR AND GLUCOCORTICOID RECEPTOR MODULATORS

The present invention relates to novel dihydropyridine derivatives of formula (I): as modulators of nuclear receptors selected from androgen receptor and glucocorticoid receptor, to processes for their preparation, to pharmaceutical compositions comprising said compounds and to the use of said for manufacturing a medicament for the treatment of pathological conditions or diseases that can improve by modulation of androgen receptor and/or glucocorticoid receptor, selected from cancer, metastasizing cancers, benign prostate hyperplasia, polycystic ovary syndrome (PCOS), hair loss, hirsutism, acne, hypogonadism, muscle wasting diseases, cachexia, Cushing's syndrome, anti-psychotic drug induced weight gain, obesity, post-traumatic stress disorder and alcoholism.

Solid-phase synthesis of pyrrolo[3,4-b]pyridines and related pyridine- fused heterocycles

Sequential Hantzsch condensation and cyclative cleavage reactions have been used to define a novel solid-phase route to pyrrolo[3,4-b]pyridines and related pyridine-fused heterocycles. A combinatorial library of ~5000 compounds prepared via this chemistry is described.

Novel 2-amino-1,4-dihydropyridine calcium antagonists. II. Synthesis and antihypertensive effects of 2-amino-1,4-dihydropyridine derivatives having N,N-dialkylaminoalkoxycarbonyl groups at 3- and/or 5-positions

Novel 2-amino-1,4-dihydropyridine derivatives I, which contain N,N-dialkylaminoalkoxycarbonyl groups at the 3- and/or 5-position, were synthesized and their antihypertensive effects were evaluated in spontaneously hypertensive rats. Remarkably prolonged duration of antihypertensive action was observed when a tertiary amino group was introduced into either the 3- or 5-ester side-chain of the 1,4-dihydropyridine ring. In particular, the compounds containing cyclic amino moieties at the 3-position showed greater potency than those with acyclic amino moieties. Chemical modification studies indicated that the two ester side-chains of 1,4-dihydropyridine at the 3- and 5-position might function in a different manner in relation to the antihypertensive activities. 3-(1-Benzhydrylazetidin-3-yl) 5-isopropyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxyl ate, I-43 (CS-905), exhibited potent and long-lasting antihypertensive effects with gradual onset of action, and is a promising candidate as an antihypertensive drug.

Calcium channel blocking and positive inotropic activities of ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfonyl)methyl]-4-aryl-3-pyrid ine-carboxylate and analogues. Synthesis and structure-activity relationships

The synthesis and pharmacological evaluation of a series of 2-[(arylsulfonyl)methyl]-4-aryl-5-cyano-1,4-dihydropyridine-3-carboxyl ic acid esters and analogues are described. These compounds possess a unique profile namely, calcium channel blocking and positive inotropic activities in vitro. Compound 54 was selected as the best compound in the series and was studied in detail. The synthesis and biological profiles of enantiomers of 54 are also reported. The data indicate that although the calcium channel blocking property of 54 is stereospecific the positive inotropic activity is not. Examples of 3- and 6-cyano and other closely related 1,4-dihydropyridine derivatives are described and evaluated for comparison and were found to be devoid of dual activities mentioned above.

Synthesis, molecular structure, and complexation of 1,4-dihydropyridines containing ligands for intramolecular complexation of metal electrophiles

A series of 4-substituted Hantzsch 1,4-dihydropyridines has been synthesized.Substituents at the 4-position include 2-pyridyl, 2-imidazolyl, and 1-methyl-2-imidazolyl.By use of various acetoacetic ester derivatives methoxy and methylthio groups have been introduced in the ester side chains at the 3,5-positions.A representative example is bis(2-methoxyethyl) 1,4-dihydro-2,6-dimethyl-4-(1H-imidazol-2-yl)-3,5-pyridinedicarboxylate (5h).The crystal structure of bis1,4-dihydro-2,6-dimethyl-4-(1H-imidazol-2-yl)-3,5-pyridinedicarboxylate (5i) has been determined.The imidazole group at the 4-position is located in a pseudo-axial position.In the 13C- and 1H-NMR spectra line doubling is seen in the 4-imidazole-substituted derivatives.This is apparently the result of slow tautomerization.Various complexes with Zn(NO3)2*4H2O have been prepared but no crystal structures could be obtained.These 1,4-dihydropyridines have little capacity, either in the presence or absence of metal ions, to carry out reductions.This may be the result of a stereoelectronic effect caused by the (presumably) equatorial orientation of the hydrogen (hydride) to be donated.

Nimodipine: Synthesis and metabolic pathway

Key step of the synthesis of the calcium antagonistic cerebral vasodilator (±) isopropyl-2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (Bay e 9736, nimodipine) is the cyclising Michael addition. A pharmacokinetic study with 14C-nimodipine in the rat revealed as major metabolites the dihydropyridines as well as the pyridines. A potential metabolic pathway is discussed involving ether cleavage and oxidation to the pyridine form as primary biotransformation steps. Reference metabolites were synthesized using 1,4-dihydropyridines with appropriate functionalities as precursors.