Home Cart 0 Sign in  

[ CAS No. 141-97-9 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 141-97-9
Chemical Structure| 141-97-9
Structure of 141-97-9 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 141-97-9 ]

Related Doc. of [ 141-97-9 ]

Alternatived Products of [ 141-97-9 ]

Product Details of [ 141-97-9 ]

CAS No. :141-97-9 MDL No. :MFCD00009199
Formula : C6H10O3 Boiling Point : -
Linear Structure Formula :- InChI Key :XYIBRDXRRQCHLP-UHFFFAOYSA-N
M.W :130.14 Pubchem ID :8868
Synonyms :
Ethyl acetoacetate

Calculated chemistry of [ 141-97-9 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.67
Num. rotatable bonds : 4
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 32.44
TPSA : 43.37 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.92 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.34
Log Po/w (XLOGP3) : 0.25
Log Po/w (WLOGP) : 0.53
Log Po/w (MLOGP) : 0.28
Log Po/w (SILICOS-IT) : 0.73
Consensus Log Po/w : 0.63

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.54
Solubility : 37.5 mg/ml ; 0.288 mol/l
Class : Very soluble
Log S (Ali) : -0.72
Solubility : 24.7 mg/ml ; 0.19 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.06
Solubility : 11.2 mg/ml ; 0.0861 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.42

Safety of [ 141-97-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P210-P261-P280-P305+P351+P338-P403+P235 UN#:N/A
Hazard Statements:H227-H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 141-97-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 141-97-9 ]
  • Downstream synthetic route of [ 141-97-9 ]

[ 141-97-9 ] Synthesis Path-Upstream   1~145

  • 1
  • [ 141-97-9 ]
  • [ 76520-25-7 ]
  • [ 1824-81-3 ]
  • [ 19013-22-0 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1980, vol. 53, # 10, p. 2891 - 2894
  • 2
  • [ 141-97-9 ]
  • [ 4344-87-0 ]
YieldReaction ConditionsOperation in experiment
96% With hydrazine In neat (no solvent) at 140℃; for 0.00555556 h; Irradiation; Green chemistry General procedure: A mixture of phenyl hydrazine (1 mmol), ethyl acetoacetate (1 mmol), and cobalt doped ZnS NPs (5 molpercent) which was taken in a Borosil beaker. The reaction mixture was homogenized with the help of a glass rod and irradiated in an infrared reactor (360 W). The progress of the reaction was checked on TLC. After completion, the reaction mixture was cooled at room temperature. The resultant material was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous MgSO4, and the solvent was evaporated under reduced pressure to yield the crude product, which was then purified by recrystallization from hot ethanol. Nanoparticles were recovered by sonication of aqueous layer and reutilized four times for the same reaction.
Reference: [1] Journal of Molecular Catalysis A: Chemical, 2013, vol. 373, p. 61 - 71
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2016, vol. 55B, # 4, p. 507 - 516
[3] Patent: WO2015/200650, 2015, A1, . Location in patent: Paragraph 0532-0534
[4] Chemische Berichte, 1896, vol. 29, p. 257
[5] Journal fuer Praktische Chemie (Leipzig), 1889, vol. <2> 39, p. 52
[6] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1952, p. 1049,1055; engl. Ausg. S. 917, 921
[7] Journal of the American Chemical Society, 1958, vol. 80, p. 599
[8] Synthesis, 2008, # 21, p. 3504 - 3508
  • 3
  • [ 3473-63-0 ]
  • [ 141-97-9 ]
  • [ 3524-87-6 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 6, p. 1601 - 1606
  • 4
  • [ 75-21-8 ]
  • [ 141-97-9 ]
  • [ 517-23-7 ]
Reference: [1] Australian Journal of Chemistry, 1993, vol. 46, # 11, p. 1657 - 1672
[2] Patent: US5183908, 1993, A,
  • 5
  • [ 96-48-0 ]
  • [ 141-52-6 ]
  • [ 141-78-6 ]
  • [ 517-23-7 ]
  • [ 1071-73-4 ]
  • [ 999-10-0 ]
  • [ 25560-91-2 ]
  • [ 141-97-9 ]
  • [ 65652-24-6 ]
Reference: [1] Pharmaceutical Chemistry Journal, 1988, vol. 22, # 12, p. 911 - 915[2] Khimiko-Farmatsevticheskii Zhurnal, 1988, vol. 22, # 12, p. 1465 - 1469
  • 6
  • [ 141-97-9 ]
  • [ 2450-71-7 ]
  • [ 1721-26-2 ]
Reference: [1] Organic Letters, 2011, vol. 13, # 16, p. 4184 - 4187
  • 7
  • [ 141-97-9 ]
  • [ 107-02-8 ]
  • [ 1721-26-2 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 10, p. 2140 - 2149
  • 8
  • [ 141-97-9 ]
  • [ 1721-26-2 ]
Reference: [1] Chemische Berichte, 1941, vol. 74, p. 1111,1114
[2] Chemical Communications, 2014, vol. 50, # 82, p. 12270 - 12272
  • 9
  • [ 141-97-9 ]
  • [ 2199-51-1 ]
Reference: [1] Patent: CN108191835, 2018, A,
  • 10
  • [ 31915-82-9 ]
  • [ 141-97-9 ]
  • [ 2199-51-1 ]
Reference: [1] Chemische Berichte, 1957, vol. 90, p. 79,81
  • 11
  • [ 7664-41-7 ]
  • [ 141-97-9 ]
  • [ 78-95-5 ]
  • [ 2199-51-1 ]
  • [ 2199-52-2 ]
Reference: [1] Journal of the American Chemical Society, 1948, vol. 70, p. 739
[2] Journal of the American Chemical Society, 1951, vol. 73, p. 356
  • 12
  • [ 141-97-9 ]
  • [ 306-44-5 ]
  • [ 2199-51-1 ]
Reference: [1] Chemische Berichte, 1902, vol. 35, p. 3004
[2] Chemische Berichte, 1902, vol. 35, p. 3004
  • 13
  • [ 141-97-9 ]
  • [ 51135-73-0 ]
Reference: [1] Letters in Drug Design and Discovery, 2016, vol. 13, # 9, p. 912 - 920
  • 14
  • [ 5436-21-5 ]
  • [ 141-97-9 ]
  • [ 3284-51-3 ]
Reference: [1] Journal of the American Chemical Society, 2002, vol. 124, # 38, p. 11228 - 11229
[2] Tetrahedron, 2001, vol. 57, # 23, p. 4867 - 4871
  • 15
  • [ 141-97-9 ]
  • [ 3284-51-3 ]
Reference: [1] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1944, vol. 280, p. 123,125
  • 16
  • [ 603-69-0 ]
  • [ 35691-93-1 ]
  • [ 141-97-9 ]
  • [ 1068-57-1 ]
Reference: [1] Russian Journal of Organic Chemistry, 1994, vol. 30, # 10, p. 1630 - 1636[2] Zhurnal Organicheskoi Khimii, 1994, vol. 30, # 10, p. 1548 - 1553
[3] Russian Journal of Organic Chemistry, 1994, vol. 30, # 10, p. 1630 - 1636[4] Zhurnal Organicheskoi Khimii, 1994, vol. 30, # 10, p. 1548 - 1553
[5] Russian Journal of Organic Chemistry, 1994, vol. 30, # 10, p. 1630 - 1636[6] Zhurnal Organicheskoi Khimii, 1994, vol. 30, # 10, p. 1548 - 1553
  • 17
  • [ 1120-90-7 ]
  • [ 141-97-9 ]
  • [ 39931-77-6 ]
Reference: [1] Chemical Communications, 2013, vol. 49, # 60, p. 6767 - 6769
  • 18
  • [ 141-97-9 ]
  • [ 58052-80-5 ]
  • [ 75-07-0 ]
  • [ 37669-78-6 ]
Reference: [1] Chemische Berichte, 1885, vol. 18, p. 2022
  • 19
  • [ 593-67-9 ]
  • [ 141-97-9 ]
  • [ 75-07-0 ]
  • [ 1721-13-7 ]
  • [ 37669-78-6 ]
Reference: [1] Journal of the Chemical Society, Dalton Transactions: Inorganic Chemistry (1972-1999), 1997, # 11, p. 1815 - 1820
  • 20
  • [ 2976-86-5 ]
  • [ 141-97-9 ]
  • [ 37669-78-6 ]
Reference: [1] Doklady Akademii Nauk SSSR, 1951, vol. 79, p. 609,611[2] Chem.Abstr., 1955, p. 15894
  • 21
  • [ 141-97-9 ]
  • [ 95-54-5 ]
  • [ 52099-72-6 ]
YieldReaction ConditionsOperation in experiment
94% With sodium hydroxide In o-xylene at 130℃; for 7 h; 50 grams of o-phenylenediamine,90 g of ethyl acetoacetate and 5 g of sodium hydroxide were dissolved in 300 ml of o-xylene.Warming up to 130 ° C,The water was refluxed for about 7 hours.Cooled to 80 ° C,Wash twice with 100 ml of water,Cooled to 0 ° C,Precipitating a white solid,filter,Drying gives 65 grams of compound (DOM-2),The yield was 94percent.
87.9% With potassium hydroxide In 5,5-dimethyl-1,3-cyclohexadiene; ethanol for 2 h; Reflux In a three-necked reaction flask equipped with a water separator,54.0 g (0.5 mol) of o-phenylenediamine and 220 mL of xylene were added,5 mL of potassium hydroxide in ethanol (where the weight of potassium hydroxide was 1.0 g)After heating and stirring,A mixture of 71.5 g (0.55 mol) of ethyl acetoacetate and 20 mL of xylene was slowly added dropwise,After dripping, stir the mixture to azeotropic dehydration to the presence of no water,And then continue to stir reflux 2h.Reaction completed, cooling, precipitation crystallization, filtration,Dried to give 76.5 g of white granules (yield 87.9percent) of 1-isopropenylbenzimidazolone
18% at 150℃; for 1 h; 1-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one (Intermediate): [Show Image] A solution of benzene-1,2-diamine (1.0 g, 9.26 mmol) in ethyl acetoacetate (1.18 mL, 9.26 mol) was heated at 150°C for 1 h. The solvent was removed on vacuo and the residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 6/4) to afford a yellow solid (290 mg, 18percent). 1H NMR (400 MHz, CDCl3) δ 7.09 (m, 4H, Ar), 5.41 (s, 1H, H2C=C), 5.25 (s, 1H, H2C=C), 2.25 (s, 3H, C=CCH3).LC/MS (ES+) m/z 175.1 (M+H)+
Reference: [1] Patent: CN108129396, 2018, A, . Location in patent: Paragraph 0022; 0023; 0033; 0034
[2] Bulletin des Societes Chimiques Belges, 1987, vol. 96, # 10, p. 787 - 792
[3] Patent: CN102816121, 2016, B, . Location in patent: Paragraph 0022-0024
[4] Journal of Chemical Research - Part S, 1996, # 2, p. 92 - 93
[5] Russian Journal of Physical Chemistry A, 2015, vol. 89, # 5, p. 807 - 811[6] Zh. Fiz. Khim.,
[7] Tetrahedron Letters, 1995, vol. 36, # 9, p. 1387 - 1390
[8] Organic Process Research and Development, 2016, vol. 20, # 9, p. 1576 - 1580
[9] European Journal of Medicinal Chemistry, 1992, vol. 27, # 8, p. 779 - 789
[10] Patent: EP1997381, 2008, A1, . Location in patent: Page/Page column 38
[11] Tetrahedron, 1992, vol. 48, # 37, p. 7863 - 7868
[12] Patent: US2008/103130, 2008, A1, . Location in patent: Page/Page column 7; 43
[13] Patent: WO2008/44127, 2008, A1, . Location in patent: Page/Page column 79
  • 22
  • [ 141-97-9 ]
  • [ 95-54-5 ]
  • [ 52099-72-6 ]
  • [ 81128-80-5 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1981, vol. 18, p. 85 - 89
  • 23
  • [ 141-97-9 ]
  • [ 95-54-5 ]
  • [ 6276-48-8 ]
  • [ 52099-72-6 ]
Reference: [1] Helvetica Chimica Acta, 1960, vol. 43, p. 1298 - 1313
[2] Journal of the Chemical Society, 1942, p. 303
  • 24
  • [ 56-23-5 ]
  • [ 141-97-9 ]
  • [ 95-54-5 ]
  • [ 52099-72-6 ]
Reference: [1] Helvetica Chimica Acta, 1960, vol. 43, p. 1298 - 1313
[2] Journal of the Chemical Society, 1960, p. 308,312
  • 25
  • [ 5271-67-0 ]
  • [ 141-97-9 ]
  • [ 13669-10-8 ]
Reference: [1] Patent: US2710867, 1954, ,
[2] Patent: US2710867, 1954, ,
  • 26
  • [ 141-97-9 ]
  • [ 22900-83-0 ]
Reference: [1] Russian Journal of General Chemistry, 2016, vol. 86, # 7, p. 1722 - 1729[2] Zh. Obshch. Khim., 2016, vol. 86, # 7, p. 1722 - 1729,8
[3] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1625 - 1629
  • 27
  • [ 1570-45-2 ]
  • [ 141-78-6 ]
  • [ 26377-17-3 ]
  • [ 141-97-9 ]
YieldReaction ConditionsOperation in experiment
87% With lithium hexamethyldisilazane In tetrahydrofuran at -40℃; for 0.333333 h; Inert atmosphere General procedure: To the solution of ester (10 mmol) in THF (20 mL) and ethyl acetate (70 mmol), LiHMDS (30 mmol) was added very quickly at -40 °C, and stirred at this temperature for 20 min. After completion of the reaction, reaction mixture was quenched with acetic acid (50 mmol) and then basified using 10percent NaHCO3 solution, extracted with ethyl acetate (2.x.100 mL), the combined organic layer was washed with water and brine solution and dried over Na2SO4. The specific purification procedure for each compound has been included along with their characterization data.
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 12, p. 4193 - 4197
  • 28
  • [ 141-97-9 ]
  • [ 2199-59-9 ]
Reference: [1] Patent: WO2011/119777, 2011, A2,
[2] Patent: CN108191835, 2018, A,
  • 29
  • [ 2524-52-9 ]
  • [ 141-78-6 ]
  • [ 26510-52-1 ]
  • [ 141-97-9 ]
YieldReaction ConditionsOperation in experiment
78% With lithium hexamethyldisilazane In tetrahydrofuran at -40℃; for 0.333333 h; Inert atmosphere General procedure: To the solution of ester (10 mmol) in THF (20 mL) and ethyl acetate (70 mmol), LiHMDS (30 mmol) was added very quickly at -40 °C, and stirred at this temperature for 20 min. After completion of the reaction, reaction mixture was quenched with acetic acid (50 mmol) and then basified using 10percent NaHCO3 solution, extracted with ethyl acetate (2.x.100 mL), the combined organic layer was washed with water and brine solution and dried over Na2SO4. The specific purification procedure for each compound has been included along with their characterization data.
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 12, p. 4193 - 4197
  • 30
  • [ 26214-65-3 ]
  • [ 141-97-9 ]
  • [ 36878-91-8 ]
Reference: [1] Zhurnal Obshchei Khimii, 1959, vol. 29, p. 3760; engl. Ausg. S. 3719
  • 31
  • [ 108-73-6 ]
  • [ 141-97-9 ]
  • [ 1013-69-0 ]
Reference: [1] J. Maharaja Sayajirao Univ. Baroda, 1955, vol. 4, # 2, p. 1,2, 5
  • 32
  • [ 141-97-9 ]
  • [ 108-46-3 ]
  • [ 14003-96-4 ]
Reference: [1] Dyes and Pigments, 2013, vol. 99, # 1, p. 1 - 5
  • 33
  • [ 106-60-5 ]
  • [ 141-97-9 ]
  • [ 38664-17-4 ]
  • [ 38664-16-3 ]
Reference: [1] Tetrahedron, 1993, vol. 49, # 32, p. 7017 - 7026
  • 34
  • [ 141-97-9 ]
  • [ 74-89-5 ]
  • [ 106-51-4 ]
  • [ 15574-49-9 ]
Reference: [1] Journal of Medicinal Chemistry, 2002, vol. 45, # 14, p. 3094 - 3102
  • 35
  • [ 141-97-9 ]
  • [ 15574-49-9 ]
Reference: [1] Patent: CN106946761, 2017, A,
[2] Letters in Drug Design and Discovery, 2018, vol. 15, # 1, p. 70 - 83
[3] Patent: WO2018/31662, 2018, A1,
  • 36
  • [ 141-97-9 ]
  • [ 89-98-5 ]
  • [ 17356-08-0 ]
  • [ 301359-45-5 ]
YieldReaction ConditionsOperation in experiment
86% With nanometasilica disulfuric acid In neat (no solvent) at 80℃; for 0.25 h; Green chemistry General procedure: Nanometasilica disulfuric acid (NMSDSA) (10 mol percent;0.024 g) or nanometasilica monosulfuric acid sodium salt(NMSMSA) (10 mol percent; 0.018 g) as a green mild catalystwas added to a mixture of aromatic aldehydes (1 mmol), ethylacetoacetate (1 mmol; 0.132 g) and urea (1.5 mmol; 0.090)or thiourea (1.5 mmol; 0.114) in a round-bottomed flask, andthe subsequent mixture was firstly stirred magnetically undersolvent-free conditions at 80 °C. After completion of the reaction,as checked by TLC n-hexane/ethyl acetate (5:2), ethylacetate (10 mL) was added to a reaction mixture, stirred andrefluxed for 5 min, and then was washed with water (10 mL)and decanted to separate catalyst from the reaction mixture(the reaction mixture was soluble in hot ethyl acetate andNMSDSA or NMSMSA catalyst was soluble in water). Thesolvent of organic layer was evaporated, and the crude productwas purified via recrystallization from ethanol/water (10:1).
85% at 100℃; for 0.5 h; Green chemistry General procedure: A mixture of aldehyde 1 (2 mmol), 1,3-dicarbonyl compounds (ethyl acetoacetate or acetylacetone, 2 mmol), urea or thiourea (2.4 mmol), and β-CD-PSA (0.02 mmol) was stirred at 100 °C for the appropriate time (monitored by TLC). Then, water (5 mL) was added and the reaction mixture filtered. The solution of β-CD-PSA was dried under vacuum for recycling catalyst in next run. Pure 3,4-dihydropyrimidinones were afforded by evaporation of the solvent followed by recrystallization from ethanol. All were characterized by spectral data and comparison of their physical data with the literature.
85% With Punica granatum peel In neat (no solvent) at 100℃; for 0.25 h; Green chemistry General procedure: To a mixture of benzaldehyde (1 mmol, 0.106 g), ethyl acetoacetate (1 mmol,0.130 g) and Punica granatum peel (0.03 g) at 100 °C, urea (1 mmol, 0.060 g) was added with stirring. The progress of the reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, the reaction mixture was cooled to room temperature. Then, cold distilled water (5 mL) was poured into the reaction flask, and the resultant mixture was decanted. The brown precipitate was dissolved in hot EtOH (3 mL) and the catalyst was separated by filtration. Then, the filtrate was distilled under reduced pressure and finally the crude product was recrystallized by EtOH to give the pure product (0.247 g, 95percent).
84% With bis(p-sulfoanilino)triazine-functionalized silica-coated magnetite nanoparticles In neat (no solvent) at 100℃; for 1.25 h; General procedure: A mixture of aromatic aldehyde (1 mmol), b-keto ester or dimedone (1 mmol) and urea or thiourea (1.2 mmol) was stirred in presence MNPs-BSAT (20 mg) at 100 °C under solvent-free condition for the appropriate time (Scheme 1). After completion of the reaction as indicated by TLC (using n-hexane-ethyl acetate as eluent), the resulting mixture was diluted with hot ethanol (15 mL) and the catalyst separated by an external magnet and washed with hot ethanol (5 mL) two times. The filtrate was cooled to room temperature and the crude products which precipitated were collected and recrystallized from ethanol if necessary.
81% With cellulose sulfuric acid In water at 100℃; for 5 h; General procedure: General procedure for the synthesis of DHPMs (4a-4m)
A mixture of aromatic aldehyde (0.01 moles), ethyl acetoacetate (0.012 moles) and urea (0.01 moles) was stirred in water at 100 °C utilizing CSA (0.05 g) for 3.5-6.5 h, the reaction was monitored by thin layer chromatography (TLC) [6:4 hexane:ethyl acetate].
After the completion of reaction, the reaction mixture was cooled and washed with ice cooled water and the solid precipitate was separated by filtration and dried in vacuum, which was passed over a column of silica gel (60-100 mesh) and then recrystallized from methanol.
81% With phenylacetic acid coated Fe3O4, sulfonated In neat (no solvent) at 20℃; for 2.58333 h; General procedure: In a typical procedure, a mixture of aldehyde (1 mmol), ethylacetoacetate (1 mmol), urea (or thiourea) (1.2 mmol) and Fe3O4/PAA-SO3H (0.06 g) was placed in a round-bottom flask. The suspension was stirred at room temperature. Completion of the reaction was monitored by Thin Layer Chromatography (TLC). After completion of the reaction, the catalyst was separated from the solid crude product using an external magnet. The precipitated solid was then collected and recrystallized from ethanol to afford the pure product.The product was identified with 1H NMR, 13C NMR and FT-IR spectroscopy techniques.
72% With sulfuric acid In ethanol at 80℃; for 3 h; General procedure: Ethyl acetoacetate (2.6mmol), different aromatic aldehydes (2.5mmol), urea (2.6mmol), few drops of sulfuric acid and 13ml ethanol were mixed together. The reaction mixure was refluxed at 80°C for 3h, then cooled to room temperature and poured into crushed ice. The precipitate was filtered & finally washed with cold water. The derivatives were recrystallized with acetonitrile to get K10–17 compounds.
66% at 90℃; for 12 h; Green chemistry General procedure: In a 25 mL roundbottom flask located with aldehyde (0.3 mmol), ethyl acetoacetate (0.3 mmol), and thiourea(0.45 mmol) was added EL (2 mL) and TMSCl (0.45 mmol). The mixture was heated at 90 C for 12 h (TLC). After being cooled down to room temperature, water (10 mL) wasadded and the resulting mixture was extracted with (3 × 10 mL) ethyl acetate. The organicphases were combined and dried over anhydrous Na2SO4. The solid was filtered out andthe solution was subjected to vacuum evaporation to remove solvent. Finally, the residuewas subjected to silica column chromatography (V3:1 of petroleum ether and ethyl acetateas eluent) to give the pure product.
40% With 1-sulfonic acid-3,5,7-trimethylpurinium-5,7-dione hydrogen sulfate In neat (no solvent) at 50℃; for 5 h; Ionic liquid; Green chemistry General procedure: A mixture of an aromatic aldehyde (1.0 mmol), ethylacetoacetate (1.0 mmol, 0.13 mL) or acetylacetone (1.0mmol, 0.1 mL), urea(1.2 mmol, 0.072 g), or thiourea (1.2mmol, 0.086 g), and [Simp]HSO4 (0.01 mmol, 0.004 g) washeated at 50 °C for an appropriate time (Table 3). Aftercompletion of the reaction, the residue was washed withwater for several times. The filtrate was recrystallized fromethanol to afford the pure product.

Reference: [1] Synthetic Communications, 2013, vol. 43, # 11, p. 1477 - 1483
[2] Chinese Journal of Chemistry, 2011, vol. 29, # 9, p. 1863 - 1868
[3] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2007, vol. 46, # 12, p. 2045 - 2048
[4] Synthetic Communications, 2009, vol. 39, # 5, p. 880 - 886
[5] Tetrahedron Letters, 2009, vol. 50, # 24, p. 2889 - 2892
[6] New Journal of Chemistry, 2016, vol. 40, # 12, p. 10412 - 10417
[7] Journal of Chemical Research - Part S, 2003, # 9, p. 601 - 602
[8] Chinese Chemical Letters, 2011, vol. 22, # 3, p. 318 - 321
[9] Catalysis Letters, 2012, vol. 142, # 12, p. 1505 - 1511
[10] Journal of Heterocyclic Chemistry, 2003, vol. 40, # 5, p. 879 - 883
[11] Journal of the Iranian Chemical Society, 2017, vol. 14, # 1, p. 121 - 134
[12] Tetrahedron, 2015, vol. 71, # 29, p. 4830 - 4834
[13] Research on Chemical Intermediates, 2017, vol. 43, # 5, p. 3325 - 3347
[14] Research on Chemical Intermediates, 2018, vol. 44, # 7, p. 4083 - 4101
[15] Journal of Molecular Catalysis A: Chemical, 2013, vol. 370, p. 197 - 204
[16] Catalysis Communications, 2013, vol. 42, p. 104 - 108
[17] New Journal of Chemistry, 2017, vol. 41, # 14, p. 6893 - 6901
[18] Bulletin of the Korean Chemical Society, 2010, vol. 31, # 6, p. 1715 - 1718
[19] Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 2011, vol. 41, # 9, p. 1135 - 1140
[20] Applied Organometallic Chemistry, 2017, vol. 31, # 4,
[21] Synthetic Communications, 2006, vol. 36, # 4, p. 451 - 456
[22] Chemical Papers, 2011, vol. 65, # 6, p. 829 - 834
[23] Bioorganic Chemistry, 2016, vol. 68, p. 265 - 274
[24] Synthetic Communications, 2006, vol. 36, # 1, p. 129 - 136
[25] Phosphorus, Sulfur and Silicon and the Related Elements, 2014, vol. 189, # 6, p. 791 - 795
[26] Tetrahedron Letters, 2007, vol. 48, # 33, p. 5777 - 5780
[27] Croatica Chemica Acta, 2017, vol. 90, # 1,
[28] Catalysis Science and Technology, 2014, vol. 4, # 1, p. 71 - 80
[29] Indian Journal of Heterocyclic Chemistry, 2010, vol. 19, # 3, p. 273 - 276
[30] Tetrahedron Letters, 2013, vol. 54, # 14, p. 1862 - 1865
[31] Chemical Communications, 2014, vol. 50, # 88, p. 13555 - 13558
[32] Chinese Chemical Letters, 2017, vol. 28, # 5, p. 1074 - 1078
[33] European Journal of Medicinal Chemistry, 2017, vol. 138, p. 140 - 151
[34] Letters in Organic Chemistry, 2018, vol. 15, # 4, p. 241 - 245
  • 37
  • [ 1147550-11-5 ]
  • [ 141-97-9 ]
  • [ 89-98-5 ]
  • [ 301359-45-5 ]
YieldReaction ConditionsOperation in experiment
90% at 110℃; for 1 h; General procedure: A mixture of aldehyde (4 mmol), β-ketoester (4 mmol), and ammonium thiocyanate (4.8 mmol) was heated at 110 °C. The reaction was monitored by thin layer chromatography. After completion of the reaction, the mixture was cooled to room temperature and quenched with water (5 mL); solid precipitated was filtered at vacuum pump, washed with water (3 X 5 mL), dried under vacuum and recrystallized from methanol and acetone (8:2) to afford the pure products
Reference: [1] Tetrahedron Letters, 2017, vol. 58, # 18, p. 1778 - 1780
  • 38
  • [ 119128-13-1 ]
  • [ 141-97-9 ]
  • [ 21881-77-6 ]
  • [ 21829-28-7 ]
  • [ 39562-70-4 ]
Reference: [1] Archiv der Pharmazie, 1989, vol. 322, # 5, p. 253 - 256
  • 39
  • [ 141-97-9 ]
  • [ 99-61-6 ]
  • [ 14205-39-1 ]
  • [ 21881-77-6 ]
  • [ 21829-28-7 ]
  • [ 39562-70-4 ]
Reference: [1] Archiv der Pharmazie, 1989, vol. 322, # 5, p. 253 - 256
  • 40
  • [ 141-97-9 ]
  • [ 3535-37-3 ]
  • [ 4687-37-0 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 2005, vol. 53, # 24, p. 9566 - 9570
[2] Pharmaceutical Chemistry Journal, 1988, vol. 22, # 1, p. 26 - 30[3] Khimiko-Farmatsevticheskii Zhurnal, 1988, vol. 22, # 1, p. 35 - 39
  • 41
  • [ 141-97-9 ]
  • [ 108-45-2 ]
  • [ 19840-99-4 ]
YieldReaction ConditionsOperation in experiment
65% at 150℃; for 20 h; General procedure: 1,3-Diaminobenzene (1.0 g, 9.3 mmol), was added to substituted ethyl acetoacetates (1.2 equiv, 2-3, 6) and the mixture was refluxed for 20 h. It was then poured on ice (100 g) and the precipitate was filtered. The product was obtained through column chromatography using silica gel (100-200 mesh) in methanol/chloroform (1:99).
38% at 130℃; for 30 h; Inert atmosphere A mixture of 1,3-phenylenediamine (19.7 g,182.0  mmol) and ethyl acetoacetate (23.7 g, 182.0 mmol) was heated at 130 °C for 30 h under an argon atmosphere. After cooling to room temperature, yellowish green solid thus precipitated was collected. Recrystallization from methanol (40 mL) yielded needle crystals (11.9 g, 38 percent). 1H NMR (DMSO-d6, 270 MHz): d 2.27 (s, 3H), 5.72 (br s, 2H), 5.93 (s, 1H), 6.35 (d, J = 2.2 Hz, 1H), 6.44 (dd, J = 8.7, 2.2 Hz, 1H), 7.33 (d, J = 8.7Hz, 1H), 11.25 (s, 1H).
Reference: [1] Medicinal Chemistry Research, 2013, vol. 22, # 11, p. 5227 - 5235
[2] Medicinal Chemistry Research, 2010, vol. 19, # 2, p. 193 - 209
[3] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 4, p. 1624 - 1638
[4] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 24, p. 8712 - 8728
[5] Journal of Medicinal Chemistry, 2016, vol. 59, # 4, p. 1648 - 1653
[6] Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 6, p. 1031 - 1034
[7] Inorganica Chimica Acta, 2010, vol. 363, # 14, p. 4048 - 4058
[8] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 17, p. 5143 - 5146
[9] Journal of Organic Chemistry, 1991, vol. 56, # 3, p. 980 - 983
[10] ChemMedChem, 2010, vol. 5, # 1, p. 103 - 117
[11] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 24, p. 7410 - 7413
[12] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 5, p. 713 - 716
[13] Tetrahedron Letters, 1999, vol. 40, # 24, p. 4505 - 4506
[14] Collection of Czechoslovak Chemical Communications, 2006, vol. 71, # 9, p. 1333 - 1349
[15] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 18, p. 8713 - 8718
[16] European Journal of Medicinal Chemistry, 2013, vol. 63, p. 589 - 602
[17] Chinese Journal of Chemistry, 2015, vol. 33, # 12, p. 1353 - 1358
[18] Bioconjugate Chemistry, 2016, vol. 27, # 10, p. 2540 - 2548
[19] Acta Poloniae Pharmaceutica - Drug Research, 2018, vol. 75, # 4, p. 903 - 910
  • 42
  • [ 141-97-9 ]
  • [ 60-34-4 ]
  • [ 5203-77-0 ]
YieldReaction ConditionsOperation in experiment
74% at 20℃; for 0.0833333 h; 3.16
1-Methyl-1H-pyrazol-5-ol (25a)
A solution of methylhydrazine (2b) (0.57 mL, 10.9 mmol) in PhMe (2 mL) was added dropwise to a solution of ethyl acetoacetate (24) (1.39 mL, 10.9 mmol) in PhMe (3 mL).
The mixture was stirred at room temperature for 5 min and then evaporated in vacuo.
Purification by recrystallization (MeOH/EtOAc) gave the title compound (0.90 g, 74percent) as a pale yellow solid, mp 112-115 °C (lit.
48
mp 112.5-113.5 °C) (found: 113.0709. C5H9N2O [MH] requires 113.0709); FTIR (KBr)/cm-1 νmax 1549, 1269, 1185, 1034; 1H NMR (400 MHz; CDCl3) δ 3.21 (3H, s, Me), 3.11 (2H, s, CH2), 2.02 (3H, s, 3-Me); 13C NMR (100 MHz, CDCl3) δ 172.2 (C), 155.5 (C), 41.4 (CH2), 31.0 (Me), 16.9 (Me); LRMS (APcI) m/z (rel intensity) 113 (MH+, 100).
61% at 80℃; for 5 h; Reflux General procedure: A solution of ethyl acetoacetate or benzoylacetate (0.01 mol) in 20 mL ethanol was added to the methylhydrazine (0.02 mol) dropwise under the ice bath. Then the mixture was refluxed at 80 °C for 5 h. After cooling, filtered and dried the precipitate. The solid obtained was pure and did not need recrystallization. The compound 2a obtained gave the yield of 61percent, and the melting point of 2a was determined as 211-212 °C, which was reported as 213 °C in the reference [13]. The compound 2b obtained gave the yield of 67 percent, and the melting point of 2b was determined as 117-118 °C (116-117 °C was reported in the reference [17]).
Reference: [1] Tetrahedron, 2013, vol. 69, # 39, p. 8429 - 8438
[2] Letters in Drug Design and Discovery, 2016, vol. 13, # 8, p. 800 - 808
[3] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 10, p. 2590 - 2594
  • 43
  • [ 141-97-9 ]
  • [ 20485-39-6 ]
Reference: [1] Patent: WO2013/163889, 2013, A1,
  • 44
  • [ 141-97-9 ]
  • [ 60-34-4 ]
  • [ 2749-59-9 ]
YieldReaction ConditionsOperation in experiment
100% at 0 - 60℃; for 16 h; Inert atmosphere To a solution of ethyl 3-oxohexanoate (11.06 g, 84.99 mmol) in anhydrous ethanol (100 mL) was added slowly methyl hydrazine (4.47 mL, 84.99 mmol) at 0 °C. The reaction was allowed to be warmed up to room temperature for 3.5 hrs. The mixture was further heated at 60 °C for 10 hrs. and kept reflux for 2.5 hrs. Reaction mixture was concentrated on rotavapor to dryness to provide intermediate 4 as a viscous pink solid (9.52 g, 100percent).1H NMR (400 MHz, CDCl3) δ (ppm): 5.06 (s, 1H), 3.85 (bs, 1H), 3.32 (s, 3H), 1.94 (s, 3H). MS (ESI): Calcd for C5H9N2O: 113.1, found: 113.2 (M+H)+.
66% at 0 - 60℃; for 3 h; Ethyl acetoacetate (15.1 mL, 119 mmol) in EtOH (200 mL) was treated at 0 °C with methyl-hydrazine (5.00 g, 109 mmol). The mixture was allowed to slowly warm to ambient temperature and then heated to 60 °C (3 h). The solvent was removed under vacuum and the residue purified by column chromatography on silica gel (EtOAc:hexanes; 1 : 1) to afford 2 (8.02 g, 71.5 mmol, 66percent yield) after purification by crystallization (DCM and hexanes) as a white off solid. 1H-NMR (400 (0258) MHz) CDC13: 3.25 (s, 3H), 3.16 (s, 2H), 2.08 (s, 3H), 13C-NMR (100 MHz) CDC13: 172.2, 155.4, 138.0, 41.3, 31.0, 16.8. LC/MS-MS: 113.2 -> 82.0 m/z; GS1 and GS2 at 30, DP = 61, CE = 25, CXP = 4, tR = 2.9 min
66% at 0 - 60℃; for 3 h; Ethyl acetoacetate (15.1 mL, 119 mmol) in EtOH (200 mL) was treated at 0 °C with methyl-hydrazine (5.00 g, 109 mmol). The mixture was allowed to slowly warm to ambient temperature and then heated to 60 °C (3 h). The solvent was removed under vacuum and the residue purified by column chromatography on silica gel (EtOAc:hexanes; 1:1) to afford 4 (8.02 g, 71.5 mmol, 66percent yield) after purification by crystallization (DCM and hexanes) as a white off solid. 1H-NMR (400 MHz) CDCl3: 3.25 (s, 3H), 3.16 (s, 2H), 2.08 (s, 3H), 13C-NMR (100 MHz) CDCl3: 172.2, 155.4, 138.0, 41.3, 31.0, 16.8. LC/MS-MS: 113.2 82.0 m/z; GS1 and GS2 at 30, DP = 61, CE = 25, CXP = 4, tR = 2.9 min.
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 13, p. 3307 - 3312
[2] Patent: WO2016/205460, 2016, A1, . Location in patent: Paragraph 0140-0141
[3] Patent: WO2016/7905, 2016, A1, . Location in patent: Page/Page column 37
[4] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 23, p. 5815 - 5818
[5] Patent: US4382948, 1983, A,
[6] Molecules, 2012, vol. 17, # 5, p. 5139 - 5150
[7] Phosphorus, Sulfur and Silicon and the Related Elements, 2014, vol. 189, # 4, p. 483 - 491
[8] Phosphorus, Sulfur and Silicon and the Related Elements, 2017, vol. 192, # 1, p. 34 - 41
[9] Nature, 2014, vol. 515, # 7527, p. 443 - 447
[10] European Journal of Medicinal Chemistry, 2016, vol. 116, p. 147 - 155
[11] Organic and Biomolecular Chemistry, 2018, vol. 16, # 3, p. 424 - 432
  • 45
  • [ 302-15-8 ]
  • [ 141-97-9 ]
  • [ 2749-59-9 ]
Reference: [1] Chemistry of Heterocyclic Compounds, 2006, vol. 42, # 3, p. 326 - 330
[2] Patent: US2016/243100, 2016, A1, . Location in patent: Paragraph 0222-0223
  • 46
  • [ 141-97-9 ]
  • [ 113-00-8 ]
  • [ 3977-29-5 ]
YieldReaction ConditionsOperation in experiment
52% at 20℃; for 10 h; The above compound was prepared using a previously reportedmethod with minor modifications [26] as shown in Scheme 1. To asolution of guanidine (2.02 g, 33.84 mM) in acetone/ethanol mixture(1:2), a solution of acetoacetic ester (4.40 g, 33.86 mM) in acetone/ethanol was added dropwise and the resulting solution wasstirred at room temperature for 10 h. The solid product obtainedwas separated by filtration and recrystallized from acetic acid toobtain colorless crystals.Yield: 1.36 g (52percent). 1H NMR (400 MHz, CDCl3, ppm), d: 11.09 (s,1H, OH), 5.92 (s, 2H, NH2), 5.14 (s, 1H, Ar–H), 2.14 (s, 3H, Ar–CH3).13C NMR (100 MHz, CDCl3, ppm) d: 162.3, 161.1, 155.3, 102.5, 23.9.ESI-MS calc. for C5H7N3O [M+]: 125.06; found 126.07 [M++1].
Reference: [1] Polyhedron, 2017, vol. 129, p. 141 - 148
  • 47
  • [ 50-01-1 ]
  • [ 141-97-9 ]
  • [ 3977-29-5 ]
Reference: [1] Bioorganic Chemistry, 2018, vol. 78, p. 258 - 268
  • 48
  • [ 593-85-1 ]
  • [ 141-97-9 ]
  • [ 3977-29-5 ]
Reference: [1] Journal of Heterocyclic Chemistry, 2004, vol. 41, # 3, p. 343 - 348
  • 49
  • [ 74-96-4 ]
  • [ 141-52-6 ]
  • [ 141-97-9 ]
  • [ 105-53-3 ]
  • [ 133-13-1 ]
  • [ 607-97-6 ]
Reference: [1] Journal of the American Chemical Society, 1931, vol. 53, p. 2407[2] Journal of the American Chemical Society, 1932, vol. 54, p. 388
  • 50
  • [ 109-65-9 ]
  • [ 141-97-9 ]
  • [ 1540-29-0 ]
Reference: [1] RSC Advances, 2016, vol. 6, # 3, p. 1865 - 1869
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2002, vol. 41, # 11, p. 2342 - 2345
[3] Synthetic Communications, 1994, vol. 24, # 1, p. 111 - 116
[4] Journal of the American Chemical Society, 1944, vol. 66, p. 145
[5] Acta Chemica Scandinavica (1947-1973), 1959, vol. 13, p. 608
[6] Journal of Organic Chemistry, 1950, vol. 15, p. 918,920
[7] Angewandte Chemie, 1963, vol. 75, p. 1059 - 1068
[8] Journal of pharmaceutical sciences, 1967, vol. 56, # 1, p. 80 - 86
[9] Journal of Organic Chemistry, 1961, vol. 26, p. 644 - 651
[10] Journal of the American Chemical Society, 2015, vol. 137, # 1, p. 508 - 517
  • 51
  • [ 542-69-8 ]
  • [ 141-97-9 ]
  • [ 1540-29-0 ]
Reference: [1] Journal of Organic Chemistry, 1980, vol. 45, # 5, p. 900 - 906
[2] Tetrahedron, 1987, vol. 43, # 24, p. 5899 - 5908
  • 52
  • [ 109-65-9 ]
  • [ 141-97-9 ]
  • [ 55501-16-1 ]
  • [ 1609-61-6 ]
  • [ 1540-29-0 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1987, p. 2159 - 2162
  • 53
  • [ 109-69-3 ]
  • [ 141-97-9 ]
  • [ 55501-16-1 ]
  • [ 1609-61-6 ]
  • [ 1540-29-0 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1987, p. 2159 - 2162
  • 54
  • [ 542-69-8 ]
  • [ 141-97-9 ]
  • [ 55501-16-1 ]
  • [ 1609-61-6 ]
  • [ 92238-43-2 ]
  • [ 1540-29-0 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1987, p. 2159 - 2162
  • 55
  • [ 1912-32-9 ]
  • [ 141-97-9 ]
  • [ 55501-16-1 ]
  • [ 1609-61-6 ]
  • [ 92238-43-2 ]
  • [ 1540-29-0 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1987, p. 2159 - 2162
  • 56
  • [ 109-65-9 ]
  • [ 141-97-9 ]
  • [ 1609-61-6 ]
  • [ 1540-29-0 ]
Reference: [1] Mendeleev Communications, 2002, vol. 12, # 2, p. 57 - 59
  • 57
  • [ 141-97-9 ]
  • [ 60481-51-8 ]
  • [ 18048-64-1 ]
YieldReaction ConditionsOperation in experiment
82% With potassium acetate; acetic acid In water at 120℃; for 7 h; 3,4-dimethylphenylhydrazine hydrochloride (8.7g, 50m mol), was dissolved in 100mlof glacial acetic acid, ethyl acetoacetate (6.5g, 50m mol) and sodium acetate (4.1g,50m mol) , 120 reflux reaction 7h, TLC detection of raw materials reaction completely.Evaporated under reduced pressureglacial acetic acid, was added 100ml of water, 100ml of ethyl acetate 4 times the combined ethyl acetatelayer was not over anhydrous sodium sulfate, and concentrated under reduced pressure to give 1- (3,4-dimethylphenyl) - 3- methyl-1hydrogen - pyrazol-5 (4 hydrogen) -one (8.3g, 82percent yield)
Reference: [1] Patent: CN103360317, 2016, B, . Location in patent: Paragraph 0095; 0105; 0106; 0108
  • 58
  • [ 141-97-9 ]
  • [ 13636-53-8 ]
  • [ 18048-64-1 ]
YieldReaction ConditionsOperation in experiment
64% at 100℃; for 24 h; A solution of 3,4-dimethylphenylhydrazine (7.3 g; 0.053 mol.) and ethyl acetoacetate (6.9 g; 0.053 mol.) in glacial acetic acid (50.0 mL) was stirred and heated at 100 for 24 h. The solvent was evaporated and the product purified by chromatography (silica gel, 50percent ethyl acetate/hexanes) to afford the title compound (16.8 g; 64percent). MS(ES) m/z 203 [M+H].
Reference: [1] Journal of Medicinal Chemistry, 2001, vol. 44, # 22, p. 3730 - 3745
[2] Patent: US6720345, 2004, B1, . Location in patent: Page column 10
[3] Organic and Biomolecular Chemistry, 2018, vol. 16, # 3, p. 424 - 432
[4] Advanced Synthesis and Catalysis, 2018, vol. 360, # 17, p. 3345 - 3355
  • 59
  • [ 7732-18-5 ]
  • [ 141-97-9 ]
  • [ 2760-98-7 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1896, vol. <2>54, p. 85
  • 60
  • [ 141-97-9 ]
  • [ 132712-71-1 ]
YieldReaction ConditionsOperation in experiment
98% With hydrazine hydrate In methanol for 2 h; Reflux To a suspension of hydrazine hydrate (2.6 g, 20 mmol) in methanol (5 mL), 3-keto-ethyl butanoate (1.0 g, 20 mmol) was added. The reaction mixture was then refluxed for 2 h. The reaction solvent was evaporated under vacuum to afford white solid product 42 (1.92 g, 98percent); 1H NMR (CDCl3) δ 2.08 (s, 3H), 5.20 (s, 1H), 10.07 (br s, 1H).
94% With acetic acid; hydrazine In methanol at 0 - 20℃; for 1 h; Heating / reflux PREPARATION 14Preparation of 3-methyl-4-phenyl-1H-pyrazol-5-ol; To a cooled (0 0C) solution of ethyl acetoacetate (2.55 mL, 20.00 mmol) in anhydrous methanol (40 mL) was added dropwise hydrazine monohydrate (0.97 mL, 20.00 mmol). The reaction mixture was allowed to warm to ambient temperature and was then heated at reflux for 1 h. The reaction mixture was cooled to ambient temperature, concentrated in vacuo and dried under high vacuum to afford 3-methyl-4- phenyl-1H-pyrazol-5-ol as a colorless solid in 94percent yield (1.85 g): 1H NMR (300 MHz, <n="69"/>DMSO-d6) δ 10.27 (br s, 2H), 5.21 (s, 1 H), 2.08 (s, 3H); 13C NMR (75 MHz, DMSO-Cf6) δ 161.0, 139.3, 88.9, 11.2; MS (ES+) m/z 99.1 (M + 1 ).
92% With hydrazine In water at 20℃; for 0.166667 h; Green chemistry General procedure: To a mixture of dicarbonyl compounds (1.0 mmol) and hydrazines/hydrazides (1.0 mmol) Fe3O4(at)SiO2(at)PDETSA MNPs (0.005 g) was added in water (2 mL). The mixture was stirred for the appropriate time at rt, as shown in Tables 3, 4 and 5. Completion of the reaction was indicated by TLC monitoring. After completion of the reaction, Fe3O4(at)SiO2(at)PDETSA MNPs were separated by external magnet. Then, the product was extracted with ethyl acetate (2 x 10 mL). The organic layer was dried (Na2SO4) and evaporated, and the crude product was purified by flash column chromatography (ethyl acetate/n-hexane, 1:20) to provide the pure product.
1.92 g With hydrazine hydrate In methanol for 2 h; Reflux To a suspension of hydrazine hydrate (2.6 g) in methanol (5 mL) ethyl-3-oxobutanoate (1.0 g) was added. The reaction mixture was then refluxed for 2h. The reaction solvent was evaporated under vacuum to afford product 42.
17 g With hydrazine hydrate In tolueneReflux 20 g of ethyl acetoacetate was added to 130 ml of toluene,Add 26g hydrazine hydrate, reflux overnight, concentrated and then add ethyl acetate and water,Dispensing,Dry and concentrated, And the residue was separated on column to give 17 g of 3-methylpyrazol-5-ol.
22 g With hydrazine hydrate In toluene 30 g of ethyl acetoacetate was added to 190 ml of toluene, 39 g of hydrazine hydrate was added, the mixture was stirred overnight and concentrated. Ethyl acetate and water were added thereto,Separation, drying, concentration, the residue was isolated on the column 22g 3-methylpyrazol-5-ol.
22 g With hydrazine hydrate In tolueneReflux Put 30gEthyl acetoacetate was added to 190 ml of toluene, 39 g of hydrazine hydrate was added,The mixture was refluxed with stirring overnight, concentrated and then added with ethyl acetate and water. The layers were separated, dried and concentrated. The residue was separated on the column to give 22 g of 3-methylpyrazol-5-ol.
22 g With hydrazine hydrate In tolueneReflux Add 30 g of ethyl acetoacetate to 190 ml of toluene, add 39 g of hydrazine hydrate, stir and reflux overnight, concentrate and then add ethyl acetate and water, separate, dry and concentrate. The residue is separated on the column to obtain 22 g of 3-methylpyrazole -5-ol.
17 g With hydrazine hydrate In tolueneReflux 20 g of ethyl acetoacetate was added to 130 ml of toluene, 26 g of hydrazine hydrate was added, and the mixture was stirred under reflux overnight, concentrated, and then ethyl acetate and water were added, and the mixture was separated, dried and concentrated.The residue was separated on a column to give 17 g of 3-methylpyrazol-5-ol.

Reference: [1] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 9, p. 2739 - 2752
[2] Patent: WO2008/121861, 2008, A2, . Location in patent: Page/Page column 67-68
[3] RSC Advances, 2014, vol. 4, # 105, p. 61193 - 61199
[4] Research on Chemical Intermediates, 2016, vol. 42, # 4, p. 3169 - 3181
[5] Journal of the Iranian Chemical Society, 2013, vol. 10, # 2, p. 213 - 219
[6] Patent: WO2014/138979, 2014, A1, . Location in patent: Page/Page column 21; 22; 23
[7] Patent: CN106831585, 2017, A, . Location in patent: Paragraph 0018; 0019; 0020
[8] Patent: CN107235903, 2017, A, . Location in patent: Paragraph 0019; 0020
[9] Patent: CN106883177, 2017, A, . Location in patent: Paragraph 0019; 0020
[10] Patent: CN107235904, 2017, A, . Location in patent: Paragraph 0019; 0020
[11] Patent: CN108117538, 2018, A, . Location in patent: Paragraph 0018; 0019; 0020
  • 61
  • [ 141-97-9 ]
  • [ 302-01-2 ]
  • [ 132712-71-1 ]
Reference: [1] Comptes Rendus Chimie, 2013, vol. 16, # 9, p. 773 - 777
  • 62
  • [ 140-29-4 ]
  • [ 141-78-6 ]
  • [ 141-97-9 ]
  • [ 4468-48-8 ]
YieldReaction ConditionsOperation in experiment
26%
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran; water
Stage #2: at 20℃; for 0.5 h;
General procedure: Ethyl ester 1 (6.65 mmol, 1 equiv) was dissolved in THF (30 mL, technical grade involving 0.2percent water) with stirring (about 230rpm) at ambient temperature for 5min. Potassium tert-butoxide (1.57 g, 14.0 mmol, 95percent, 2 equiv) was added immediately to the above THF solution. After stirring enough the flask, the corresponding cyanide 8 (6.65mmol, 1equiv) was then added. The resulting mixture was stirred at ambient temperature. The reaction mixture was quenched by addition of water (50mL) and then stirred for 5min. After adding ethyl acetate (40 mL) and then HCl solution (1 mL, 12 M), the organic layer was separated and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was applied to the top of an open-bed silica gel column (for 9a–e, 9g–j: 3×15cm, n-hexane/ethyl acetate (3:1, v/v); for 9f: 3.5×8 cm, CH2Cl2). Fractions containing the product were combined and evaporated under reduced pressure to give the corresponding β-ketonitriles.
Reference: [1] Tetrahedron, 2013, vol. 69, # 48, p. 10331 - 10336
  • 63
  • [ 141-97-9 ]
  • [ 122-51-0 ]
  • [ 3788-94-1 ]
YieldReaction ConditionsOperation in experiment
80% at 130℃; for 5 h; 2.22 Example 22 {prepared via Scheme 12)- 6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-lH-3-benzazepin-7-yl)methyl]-2-(3-methoxyazetidin-l- yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-one . iStep a) Intermediate 25Ethyl 2-(ethoxymethylene)-3-oxobutanoate A solution of ethyl 3-oxobutanoate (20 g, 154 mmol), triethylorthoformate (51.1 ml, 307 mmol), and acetic anhydride (43.5 ml, 461 mmol) was heated at 130 °C for 5 h. The reaction was cooled to r.t. and concentrated under reduced pressure to remove triethyl orthoformate and acetic anhydride. The remainder of acetic anhydride and triethyl orthoformate was removed by distillation (30 mbar, 30-70 °C). Ethyl 2-(ethoxymethylene)-3-oxobutanoate was distilled off (6 mbar, 80 °C to 128 °C) to leave ethyl 2-(ethoxymethylene)-3-oxobutanoate as a viscous yellow oil (22.8 g, 80percent) NMR (400 MHz, CDC13) δ 7.59 - 7.69 (m, 1H), 4.17 - 4.34 (m, 4H), 2.29 - 2.44 (m, 3H), 1.25 - 1.44 (m, 6H).
79% at 130℃; for 12 h; Ethylacetoacetate (15.62 g, 0.12mol), triethylorthoformate (17.78 g, 0.12 mol), acetic anhydride (28.82 g, 0.24 mol) were mixed and heated at 130 oC for 12 hr with stirring. The product was distilled to obtain 11.4 g (79 percent) of black oil that was used directly in the next step.
70% at 135℃; A mixture of ethyl acetoacetate (100 g, 0.77 mol), friethyi orthoformate ( 130 g, 0.92 mol), and acetic anhydride ( 150 g, 1 .5 mol) was heated ai 135 °C for 6 - 18 h in a round bottomed flask that was equipped with a distillation apparatus to collect the ethanol generated during the reaction. The reaction was cooled, concentrated and the residue was distilled under high vacuum to obtain the desired product (100 g, 70percent) as a pale yellow oil: ES MS m /z 181 [M + H]+.
65% at 130℃; for 4 h; A mixture of compound 1 (10.41 g, 0.08 mol), triethyl orthoformate (14.23 g, 0.10 mol) and acetic anhydride (20.42 g, 0.20 mol) was heated at 130 °C for 4 h.
The resulting EtOH, CH3CO2CH2CH3 and remaining materials were eliminated under reduced pressure and compound 2 (9.68 g) was obtained in 65percent yield.

Reference: [1] Journal of Heterocyclic Chemistry, 2018, vol. 55, # 4, p. 946 - 950
[2] Mendeleev Communications, 2016, vol. 26, # 1, p. 54 - 56
[3] Patent: WO2011/83316, 2011, A1, . Location in patent: Page/Page column 52-53
[4] Letters in Drug Design and Discovery, 2016, vol. 13, # 9, p. 912 - 920
[5] Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3563 - 3567
[6] Patent: WO2013/109388, 2013, A2, . Location in patent: Page/Page column 141
[7] Journal of medicinal chemistry, 2000, vol. 43, # 21, p. 3995 - 4004
[8] European Journal of Medicinal Chemistry, 2016, vol. 124, p. 935 - 945
[9] Heterocycles, 2004, vol. 64, p. 177 - 191
[10] Journal of the American Chemical Society, 1952, vol. 74, p. 4889
[11] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1979, p. 464 - 471

[12] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 1875 - 1880
[13] Journal of Medicinal Chemistry, 1992, vol. 35, # 18, p. 3413 - 3422
[14] Journal of Medicinal Chemistry, 2005, vol. 48, # 4, p. 1229 - 1236
[15] Patent: US2005/96353, 2005, A1, . Location in patent: Page/Page column 21
[16] Patent: US2006/30708, 2006, A1, . Location in patent: Page/Page column 10-11
[17] Tetrahedron, 2013, vol. 69, # 40, p. 8564 - 8571
[18] Russian Journal of General Chemistry, 2013, vol. 83, # 7, p. 1330 - 1335[19] Zh. Obshch. Khim., 2013, vol. 83, # 7, p. 1330 - 1335
[20] Russian Journal of Organic Chemistry, 2017, vol. 53, # 3, p. 381 - 392[21] Zh. Org. Khim., 2017, vol. 53, # 3, p. 384 - 394,11
[22] Molecules, 2015, vol. 20, # 3, p. 4383 - 4394
[23] Journal of Medicinal Chemistry, 2016, vol. 59, # 10, p. 4488 - 4510
[24] Patent: CN106212482, 2016, A, . Location in patent: Paragraph 0031; 0032
[25] Patent: CN106135228, 2016, A, . Location in patent: Paragraph 0027-0029
[26] Patent: CN106243101, 2016, A, . Location in patent: Paragraph 0027; 0028
  • 64
  • [ 141-97-9 ]
  • [ 149-73-5 ]
  • [ 3788-94-1 ]
Reference: [1] Organic Letters, 2004, vol. 6, # 7, p. 1143 - 1146
  • 65
  • [ 141-97-9 ]
  • [ 3788-94-1 ]
Reference: [1] Organic Letters, 2009, vol. 11, # 17, p. 3934 - 3937
  • 66
  • [ 108-24-7 ]
  • [ 141-97-9 ]
  • [ 122-51-0 ]
  • [ 3788-94-1 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1897, vol. 297, p. 18
[2] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 4, p. 1311
[3] Justus Liebigs Annalen der Chemie, 1897, vol. 297, p. 18
[4] Chemische Berichte, 28 Ref. &lt;1895&gt;, 82,
[5] Patent: DE77354, , ,
[6] Patent: DE77354, , ,
  • 67
  • [ 14036-06-7 ]
  • [ 141-97-9 ]
  • [ 3788-94-1 ]
Reference: [1] Journal of Organic Chemistry, 1937, vol. 2, p. 263
  • 68
  • [ 105-36-2 ]
  • [ 5500-21-0 ]
  • [ 141-97-9 ]
  • [ 77570-31-1 ]
  • [ 24922-02-9 ]
Reference: [1] Patent: US2005/96337, 2005, A1, . Location in patent: Page/Page column 45-46
  • 69
  • [ 141-97-9 ]
  • [ 1711-06-4 ]
  • [ 33166-79-9 ]
YieldReaction ConditionsOperation in experiment
17% With sodium hydroxide; ammonium chloride In water; benzene EXAMPLE 6
Preparation of Ethyl 2-Amino-4-(m-Tolyl)-5-Thiazolecarboxylate
To a cold (5° C.) mixture of 137.5 g (1.05 mole) of ethyl acetoacetate, 175 ml. of benzene, 325 ml. of water, and 45.8 ml. of 33percent sodium hydroxide was added simultaneously 221.05 g (1.430 mole) of m-toluoyl chloride and 190 ml. of 33percent sodium hydroxide as described in Example 4.
The aqueous solution of sodium salt of ethyl m-toluoylacetoacetate was stirred with 56.3 g of ammonium chloride overnight and worked up as described in Example 4 to give 38.0 g (17percent) of crude ethyl m-toluoylacetate after a Kugelrohr distillation (95°-98° C.) at 0.05 mm Hg).
17% With sodium hydroxide; ammonium chloride In water; benzene EXAMPLE 6
Preparation of Ethyl 2-Chloro-4-(m-Tolyl)-5-Thiazolecarboxylate
To a cold (5° C.) mixture of 137.5 g (1.05 mole) of ethyl acetoacetate, 175 ml. of benzene, 325 ml. of water, and 45.8 ml. of 33percent sodium hydroxide was added simultaneously 221.05 g (1.430 mole) of m-toluoyl chloride and 190 ml. of 33percent sodium hydroxide as described in Example 4.
The aqueous solution of sodium salt of ethyl m-toluoylacetoacetate was stirred with 56.3 g of ammonium chloride overnight and worked up as described in Example 4 to give 38.0 g (17percent) of crude ethyl m-toluoylacetate after a Kugelrohr distillation (95°-98° C. at 0.05 mm Hg).
Reference: [1] Patent: US4308391, 1981, A,
[2] Patent: US4336389, 1982, A,
  • 70
  • [ 141-97-9 ]
  • [ 1711-06-4 ]
  • [ 33166-79-9 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 1621 - 1630
[2] Chemische Berichte, 1935, vol. 68, p. 227,230
  • 71
  • [ 141-97-9 ]
  • [ 313225-01-3 ]
  • [ 26510-95-2 ]
Reference: [1] Synthetic Communications, 2007, vol. 37, # 10, p. 1617 - 1625
  • 72
  • [ 141-97-9 ]
  • [ 100-07-2 ]
  • [ 2881-83-6 ]
Reference: [1] Journal of Heterocyclic Chemistry, 2016, vol. 53, # 3, p. 924 - 928
[2] Journal of Agricultural and Food Chemistry, 2005, vol. 53, # 24, p. 9566 - 9570
[3] Chinese Chemical Letters, 2010, vol. 21, # 1, p. 67 - 69
[4] Heterocycles, 2013, vol. 87, # 8, p. 1691 - 1698
  • 73
  • [ 141-97-9 ]
  • [ 4231-69-0 ]
  • [ 2881-83-6 ]
Reference: [1] Synthetic Communications, 2007, vol. 37, # 10, p. 1617 - 1625
  • 74
  • [ 141-97-9 ]
  • [ 13361-55-2 ]
  • [ 2881-83-6 ]
Reference: [1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1998, vol. 37, # 11, p. 1191 - 1193
  • 75
  • [ 1336-21-6 ]
  • [ 141-97-9 ]
  • [ 609-65-4 ]
  • [ 19112-35-7 ]
YieldReaction ConditionsOperation in experiment
15% With sodium hydroxide; sodium chloride; ammonium chloride In water; benzene EXAMPLE 5
Preparation of Ethyl 2-Amino-4-(o-Chlorophenyl)-5-Thiazolecarboxylate
To a cold (5° C.) mixture of 55.0 g (0.423 mole) of ethyl acetoacetate, 70 ml. of benzene, 18.3 ml. of 33percent sodium hydroxide, and 141 ml. of water was added simultaneously with vigorous stirring 80.0 g (0.457 mole) of o-chlorobenzoyl chloride and 76 ml. of 33percent sodium hydroxide in 1 hour.
The aqueous solution of the sodium salt of ethyl o-chlorobenzoylacetoacetate was stirred with 22.5 g (0.424 mole) of ammonium chloride for 18 hours.
The aqueous solution was then saturated with 25.0 g of sodium chloride.
At this moment, some precipitate formed which was filtered.
The analysis indicated this material was mainly the sodium salt of ethyl o-chlorobenzoylacetoacetate.
The sodium salt and the aqueous filtrate were combined and acidified with dilute hydrochloric acid.
The oil which separated was extracted with ether.
The ether solution was dried (MgSO4) and concentrated under reduced pressure.
The residue was Kugelrohr distilled to give 30.0 g of oil which contained mainly ethyl o-chlorobenzoylacetoacetate.
This material was stirred with a mixture of 7.2 g of ammonium chloride, 14 ml. of concentrated ammonium hydroxide and 150 ml. of water and worked up as described in Example 4 to give 16.6 g (15percent) of crude ethyl o-chlorobenzoylacetate which was about 92percent pure.
15% With sodium hydroxide; sodium chloride; ammonium chloride In water; benzene EXAMPLE 5
Preparation of Ethyl 2-Chloro-4-(o-Chlorophenyl)-5-Thiazolecarboxylate
To a cold (5° C.) mixture at 55.0 g (0.423 mole) of ethyl acetoacetate, 70 ml. of benzene, 18.3 ml. of 33percent sodium hydroxide, and 141 ml. of water was added simultaneously with vigorous stirring 80.0 g (0.457 mole) of o-chlorobenzoyl chloride and 76 ml. of 33percent sodium hydroxide in 1 hour as described in Example 4.
The aqueous solution of sodium salt of ethyl o-chlorobenzoylacetoacetate was stirred with 22.5 g (0.424 mole) of ammonium chloride for 18 hours.
The aqueous solution was then saturated with 25.0 g of sodium chloride.
At this moment, some precipitate formed which was filtered.
The analysis indicated this material was mainly the sodium salt of ethyl o-chlorobenzoylacetoacetate.
The sodium salt and the aqueous filtrate were combined and acidified with dilute hydrochloric acid.
The oil which separated was extracted with ether.
The ether solution was dried (MgSO4) and concentrated under reduced pressure.
The residue was Kugelrohr distilled to give 30.0 g of oil which contained mainly ethyl o-chlorobenzoylacetoacetate.
This material was stirred with a mixture of 7.2 g of ammonium chloride, 14 ml. of concentrated ammonium hydroxide and 150 ml. of water and worked up as described in Example 4 to give 16.6 g (15percent) of crude ethyl o-chlorobenzoylacetate which was about 92percent pure.
Reference: [1] Patent: US4308391, 1981, A,
[2] Patent: US4336389, 1982, A,
  • 76
  • [ 141-97-9 ]
  • [ 609-65-4 ]
  • [ 19112-35-7 ]
Reference: [1] Tetrahedron Letters, 2007, vol. 48, # 42, p. 7448 - 7451
[2] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 1621 - 1630
  • 77
  • [ 50-00-0 ]
  • [ 141-97-9 ]
  • [ 487-51-4 ]
Reference: [1] Journal of Organic Chemistry, 2007, vol. 72, # 4, p. 1458 - 1463
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1979, p. 1837 - 1846
[3] Organic and Biomolecular Chemistry, 2009, vol. 7, # 17, p. 3372 - 3378
  • 78
  • [ 141-97-9 ]
  • [ 487-51-4 ]
Reference: [1] Journal of Organic Chemistry, 1939, vol. 4, p. 266,268
[2] Journal of the American Chemical Society, 1943, vol. 65, p. 631,634
  • 79
  • [ 141-97-9 ]
  • [ 2543-57-9 ]
  • [ 487-51-4 ]
Reference: [1] Chemische Berichte, 1938, vol. 71, p. 2090
[2] Journal of the Chemical Society, 1949, p. 708,712
  • 80
  • [ 75-11-6 ]
  • [ 141-97-9 ]
  • [ 487-51-4 ]
Reference: [1] Chemische Berichte, 1905, vol. 38, p. 982
[2] Justus Liebigs Annalen der Chemie, 1909, vol. 366, p. 140
[3] Chemische Berichte, 1905, vol. 38, p. 970
[4] Chemische Berichte, 1893, vol. 26, p. 884
[5] Chemische Berichte, 1912, vol. 45, p. 2686[6] Chemische Berichte, 1922, vol. 55, p. 2479
[7] Justus Liebigs Annalen der Chemie, 1905, vol. 342, p. 336,337
  • 81
  • [ 141-97-9 ]
  • [ 78-94-4 ]
  • [ 487-51-4 ]
Reference: [1] Tetrahedron Letters, 1995, vol. 36, # 46, p. 8395 - 8398
  • 82
  • [ 110-89-4 ]
  • [ 50-00-0 ]
  • [ 141-97-9 ]
  • [ 487-51-4 ]
Reference: [1] Journal of the American Chemical Society, 1943, vol. 65, p. 631,634
  • 83
  • [ 141-97-9 ]
  • [ 106-47-8 ]
  • [ 2585-04-8 ]
Reference: [1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2007, vol. 46, # 7, p. 1203 - 1207
  • 84
  • [ 141-97-9 ]
  • [ 2971-90-6 ]
YieldReaction ConditionsOperation in experiment
91.5%
Stage #1: at 30℃; for 5 h;
Stage #2: at 10℃; for 2 h;
Stage #3: at 30℃; for 2 h;
In three 500 ml flask, 130 g of ethyl acetoacetate (1 mole), Styrene-DVB (D301T) 39 g resin, reaction at 30 5 hours, 100 ml of distilled water, stirring the ammonia released 85 g (5 mol), reacted at 10 deg.] C after 2 hours with stirring chlorine gas at 142 g (2 mol), reacted at 30 2 hours and filtered Styrene-DVB (D301 T) and the resin solid cake was washed with NaOH (10percent concentration) was washed with an aqueous solution of 100 ml, Styrene-DVB (D301T) resin is recyclable. The filtrate was distilled to remove a small amount of ethanol, allowed to stand to crystallize, filtered and dried to give the desired product 87.8 g, 91.5percent yield.
Reference: [1] Patent: CN105753776, 2016, A, . Location in patent: Paragraph 0009; 0020; 0021
  • 85
  • [ 525-76-8 ]
  • [ 141-97-9 ]
  • [ 26138-64-7 ]
Reference: [1] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 6, p. 1313 - 1321
[2] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 2, p. 445 - 448
  • 86
  • [ 141-97-9 ]
  • [ 23652-67-7 ]
Reference: [1] Organic Letters, 2011, vol. 13, # 7, p. 1754 - 1757
[2] Organic Process Research and Development, 2007, vol. 11, # 3, p. 568 - 577
  • 87
  • [ 60-35-5 ]
  • [ 141-97-9 ]
  • [ 23652-67-7 ]
Reference: [1] Journal of Organic Chemistry, 1941, vol. 6, p. 70,74
  • 88
  • [ 141-97-9 ]
  • [ 4341-76-8 ]
Reference: [1] Journal of Organic Chemistry, 2009, vol. 74, # 1, p. 158 - 162
  • 89
  • [ 109-97-7 ]
  • [ 122135-84-6 ]
  • [ 4341-76-8 ]
  • [ 141-97-9 ]
Reference: [1] Journal of Organic Chemistry, 2005, vol. 70, # 21, p. 8638 - 8641
  • 90
  • [ 141-97-9 ]
  • [ 2526-64-9 ]
  • [ 4341-76-8 ]
Reference: [1] Proceedings of the Chemical Society, London, 1961, p. 302
  • 91
  • [ 1585-74-6 ]
  • [ 141-97-9 ]
  • [ 2044-64-6 ]
Reference: [1] Organic and Biomolecular Chemistry, 2014, vol. 12, # 42, p. 8473 - 8479
  • 92
  • [ 141-97-9 ]
  • [ 1067-24-9 ]
  • [ 2044-64-6 ]
Reference: [1] Journal of the Chemical Society [Section] C: Organic, 1969, p. 2565 - 2568
  • 93
  • [ 141-97-9 ]
  • [ 4755-81-1 ]
  • [ 609-15-4 ]
Reference: [1] Green Chemistry, 2009, vol. 11, # 2, p. 275 - 278
  • 94
  • [ 107-03-9 ]
  • [ 141-97-9 ]
  • [ 41051-15-4 ]
Reference: [1] Patent: US4120956, 1978, A,
  • 95
  • [ 141-97-9 ]
  • [ 13176-46-0 ]
YieldReaction ConditionsOperation in experiment
92.54% With bromine In dichloromethane at -5 - 5℃; for 2 h; Control temperature -5 ~ 5 ° C,A mixture of ethyl acetoacetate (26.03 g) was addedWith 15 mL of dichloromethanewell mixed,35.16 g of bromine was added dropwise,Insulation reaction2h,Pass dry nitrogen lh,After decompression to constant weight,The fraction was collected by distillation at 15 ° C under reduced pressure to obtain a clear oily liquid4 - bromoacetoacetate 3 8.6 9 g, yield 92.54percent;
85% at 0℃; for 1.16667 h; Example 11 - Formula 147 - Compound 11 aIntermediate B: Ethyl 4-bromo-3-oxobutanoate To a solution of compound A (10.0 g, 76.9 mmol, 1 .0 eq) in acetic acid (30 mL) was added bromine (12.3 g, 76.9 mmol, 1 .0 eq) at 0 °C over 10 min. The mixture was stirred at 0 °C for 1 h, the solvent was removed under reduced pressure and the residue was diluted with water (50 mL). The aqueous mixture was extracted with CH2CI2 (50 mL x 3). The combined organic layers were washed with brine (60 mL x 2), dried over MgS04 and concentrated under reduced pressure to give ethyl 4-bromo-3-oxobutanoate (14.3 g, 85percent) as a yellow oil.LC-MS (Agilent): Rt 3.06 min; m/z calculated for C6H9Br03 [M+H]+ 208.97, found 209.1 .
85% at 0℃; for 1.16667 h; To a solution of compound A (10.0 g, 76.9 mmol, 1.0 eq) in acetic acid (30 mL) was added bromine (12.3 g, 76.9 mmol, 1.0 eq) at 0° C. over 10 min.
The mixture was stirred at 0° C. for 1 h, the solvent was removed under reduced pressure and the residue was diluted with water (50 mL).
The aqueous mixture was extracted with CH2Cl2 (50 mL*3).
The combined organic layers were washed with brine (60 mL*2), dried over MgSO4 and concentrated under reduced pressure to give ethyl 4-bromo-3-oxobutanoate (14.3 g, 85percent) as a yellow oil.
LC-MS (Agilent): Rt 3.06 min; m/z calculated for C6H9BrO3 [M+H]+ 208.97. found 209.1.
75% at 0℃; for 2 h; 5.0 g (38.4 mmol) of ethyl 3-oxobutanoate were dissolved in 30 ml of acetic acid and cooled to 0° C. 6.15 g (38.4 mmol) of bromine were added slowly and the reaction mixture was then stirred at 0° C. for 2 h. Water was then added, and the reaction mixture was extracted twice with ethyl acetate. The combined organic phases were washed with water and saturated aqueous sodium chloride solution. Drying over sodium sulphate and removal of the solvent gave 6.0 g (75percent of theory) of the intermediate ethyl 4-bromo-3-oxobutanoate as an oil.
49% With bromine In chloroform at 20℃; for 18 h; Intermediate (38) : Preparation of (4-chloro-2-thiophen-2-yl-thieno[2,3-d] pyrimidin-5-yl)-acetic acid ethyl ester; Step 1. Preparation of 4-bromo-3-oxo-butyric acid ethyl ester; Ethyl acetoacetate (ImI, 7.84mmol) was dissolved in chloroform, therein, bromine(0.6ml, 11.76mmol) was added. The reaction mixture was stirred at room temperature for 18 hours. Sodium sulfite solution was added to quench the reaction, and ethyl acetate was added. Organic layer was washed with water and IN HCl aqueous solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (n-hexane: ethyl acetate = 4:1) to give 800mg (yield: 49percent, colorless oil) of the target compound.[690] 1U NMR(400D, CDCI); δ 4.20(q, J=4.0Hz, 2H), 4.04(s, 2H), 3.69(s, 2H), 1.28(t, J=8.0Hz, 3H).
421 g at 20℃; for 72 h; A solution of bromine (436 g, 2.73 mol) in acetic acid (750 mL) was added to a solution of ethyl 3-oxobutanoate (355 g, 2.73 mol) in acetic acid (1000 mL). The mixturewas stirred at room temperature for 72 hours and was concentrated under reduced pressure at 45°C to remove the acetic acid. The residue was partitioned between methylene chloride (400 mL) and water (250 mL). The organic layer was washed with saturated sodium bicarbonate (2 x 300 mL), water (300 mL), brine (125 mL) and was dried over anhydrous magnesium sulfate. The solution was filtered and concentrated togive ethyl 4-bromo-3-oxobutanoate as a yellow oil (421 g).
6.0 g at 0℃; for 2 h; 73.4 g (1064 mmol) of sodium nitrite, dissolved in 520 ml of water, were added to a solution, stirred at 0° C., of 100 g (769 mmol) of ethyl 3-oxobutanoate in 250 ml of acetic acid. The reaction mixture was stirred at room temperature for 1 h. After addition of water, the mixture was extracted twice with ethyl acetate. The combined organic phases were washed with water and saturated aqueous sodium chloride solution. Drying over sodium sulphate and removal of the solvent gave 105 g (86percent of theory) of the intermediate ethyl 2-(hydroximino)-3-oxobutanoate as a colourless liquid

Reference: [1] Patent: CN105820102, 2016, A, . Location in patent: Paragraph 0029-0031
[2] Patent: WO2012/63085, 2012, A2, . Location in patent: Page/Page column 81
[3] Patent: US2013/225594, 2013, A1, . Location in patent: Paragraph 0252; 0253
[4] Canadian Journal of Chemistry, 2001, vol. 79, # 8, p. 1259 - 1271
[5] Patent: TW2016/5831, 2016, A, . Location in patent: Paragraph 0211
[6] Journal of Organic Chemistry, 2012, vol. 77, # 8, p. 3959 - 3968
[7] Journal of the American Chemical Society, 2015, vol. 137, # 35, p. 11258 - 11261
[8] Patent: WO2007/102679, 2007, A1, . Location in patent: Page/Page column 63
[9] Tetrahedron Asymmetry, 2001, vol. 12, # 12, p. 1713 - 1718
[10] Journal of Materials Chemistry, 2012, vol. 22, # 33, p. 17100 - 17112
[11] Tetrahedron Letters, 1984, vol. 25, # 31, p. 3369 - 3372
[12] Justus Liebigs Annalen der Chemie, 1891, vol. 266, p. 75
[13] Justus Liebigs Annalen der Chemie, 1894, vol. 278, p. 79
[14] Chemische Berichte, 1896, vol. 29, p. 1043
[15] Justus Liebigs Annalen der Chemie, 1882, vol. 213, p. 152,156[16] Chemische Berichte, 1883, vol. 16, p. 133
[17] Journal of Organic Chemistry, 1947, vol. 12, p. 342,351
[18] Justus Liebigs Annalen der Chemie, 1923, vol. 430, p. 104
[19] Tetrahedron, 1973, vol. 29, p. 4251 - 4258
[20] Comptes Rendus des Seances de l'Academie des Sciences, Serie C: Sciences Chimiques, 1974, vol. 278, p. 1289 - 1292
[21] Heterocycles, 1986, vol. 24, # 5, p. 1429 - 1431
[22] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 13, p. 1987 - 1995
[23] Patent: US6310095, 2001, B1,
[24] Organic and Biomolecular Chemistry, 2008, vol. 6, # 2, p. 366 - 373
[25] European Journal of Medicinal Chemistry, 2008, vol. 43, # 10, p. 2178 - 2188
[26] Journal of the Indian Chemical Society, 2008, vol. 85, # 11, p. 1163 - 1168
[27] Patent: US6809107, 2004, B1, . Location in patent: Page/Page column 66-67
[28] Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 2011, vol. 66, # 2, p. 177 - 183
[29] Patent: US2011/230461, 2011, A1, . Location in patent: Page/Page column 29
[30] Patent: WO2013/182933, 2013, A1, . Location in patent: Page/Page column 15
[31] ChemMedChem, 2013, vol. 8, # 12, p. 1923 - 1929
[32] European Journal of Medicinal Chemistry, 2014, vol. 74, p. 225 - 233
[33] ACS Medicinal Chemistry Letters, 2014, vol. 5, # 5, p. 474 - 479
[34] Polyhedron, 2014, vol. 75, p. 9 - 21
[35] RSC Advances, 2015, vol. 5, # 79, p. 64566 - 64581
[36] Synthetic Communications, 2015, vol. 45, # 19, p. 2195 - 2202
[37] European Journal of Medicinal Chemistry, 2015, vol. 105, p. 194 - 207
[38] Patent: CN105924470, 2016, A, . Location in patent: Paragraph 0169
[39] Patent: US2016/237059, 2016, A1, . Location in patent: Paragraph 0499
[40] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 4, p. 2501 - 2510
[41] European Journal of Medicinal Chemistry, 2018, vol. 150, p. 864 - 875
  • 96
  • [ 141-97-9 ]
  • [ 13176-46-0 ]
Reference: [1] Organic Letters, 2003, vol. 5, # 4, p. 411 - 414
[2] Organic Letters, 2003, vol. 5, # 4, p. 411 - 414
  • 97
  • [ 141-97-9 ]
  • [ 84911-18-2 ]
  • [ 13176-46-0 ]
  • [ 89415-67-8 ]
Reference: [1] Organic Letters, 2003, vol. 5, # 4, p. 411 - 414
  • 98
  • [ 141-97-9 ]
  • [ 84911-18-2 ]
  • [ 13176-46-0 ]
Reference: [1] Tetrahedron Letters, 2007, vol. 48, # 8, p. 1411 - 1415
  • 99
  • [ 105-36-2 ]
  • [ 13176-46-0 ]
  • [ 141-97-9 ]
Reference: [1] Chemische Berichte, 1908, vol. 41, p. 955
  • 100
  • [ 109-72-8 ]
  • [ 105-36-2 ]
  • [ 26818-07-5 ]
  • [ 13176-46-0 ]
  • [ 141-97-9 ]
  • [ 123-25-1 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1988, vol. 330, # 3, p. 497 - 500
  • 101
  • [ 141-97-9 ]
  • [ 105-36-2 ]
  • [ 1115-30-6 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 3, p. 365 - 368
[2] Monatshefte fuer Chemie, 1990, vol. 121, p. 173 - 187
[3] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1991, vol. 40, # 5.1, p. 955 - 961[4] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1991, # 5, p. 1073 - 1079
[5] Journal of Labelled Compounds and Radiopharmaceuticals, 1995, vol. 36, # 8, p. 745 - 754
[6] European Journal of Medicinal Chemistry, 2013, vol. 67, p. 39 - 53
[7] Patent: CN103450134, 2017, B, . Location in patent: Paragraph 0019; 0185; 0188
  • 102
  • [ 141-97-9 ]
  • [ 105-39-5 ]
  • [ 1115-30-6 ]
Reference: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1990, vol. 39, # 2.2, p. 412 - 413[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1990, # 2, p. 474 - 475
  • 103
  • [ 141-97-9 ]
  • [ 623-48-3 ]
  • [ 1115-30-6 ]
Reference: [1] Journal of the American Chemical Society, 2012, vol. 134, # 17, p. 7344 - 7350
  • 104
  • [ 623-73-4 ]
  • [ 141-97-9 ]
  • [ 1115-30-6 ]
  • [ 125211-68-9 ]
Reference: [1] Tetrahedron Letters, 1989, vol. 30, # 31, p. 4093 - 4096
  • 105
  • [ 141-97-9 ]
  • [ 1115-30-6 ]
Reference: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1980, vol. 29, # 1, p. 109 - 112[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1980, # 1, p. 125 - 128
  • 106
  • [ 141-97-9 ]
  • [ 1115-30-6 ]
  • [ 623-71-2 ]
  • [ 64-19-7 ]
  • [ 141-78-6 ]
  • [ 609-15-4 ]
  • [ 123-25-1 ]
Reference: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1980, vol. 29, # 1, p. 109 - 112[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1980, # 1, p. 125 - 128
  • 107
  • [ 141-97-9 ]
  • [ 7169-06-4 ]
  • [ 38480-94-3 ]
Reference: [1] Proceedings - Indian Academy of Sciences, Section A, 1953, # 38, p. 480,490
  • 108
  • [ 141-97-9 ]
  • [ 104-88-1 ]
  • [ 35271-74-0 ]
Reference: [1] Patent: US2792418, 1954, ,
[2] Journal of the American Chemical Society, 1959, vol. 81, p. 5733,5735
[3] Tetrahedron Asymmetry, 2005, vol. 16, # 14, p. 2475 - 2485
[4] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 4, p. 845 - 849
  • 109
  • [ 589-87-7 ]
  • [ 141-97-9 ]
  • [ 14062-25-0 ]
YieldReaction ConditionsOperation in experiment
50% With caesium carbonate In 1,4-dioxane at 100℃; for 12 h; General procedure: A mixture of aryl iodide (5 mmol), ethyl acetoacetate(7.5 mmol), Cu2+/4A (0.5 g, 0.1 mol percent copper) and Cs2CO3 (12.5 mmol) indioxane (10 ml) was stirred at 100 C for 12 h. The solid was filtered and thefiltrate was evaporated in vacuo. The products were purified by columnchromatography (silica gel, hexane/acetone 4:1 eluent). The products werecharacterized by 1H NMR and GC–MS.
Reference: [1] Tetrahedron Letters, 2015, vol. 56, # 46, p. 6389 - 6392
  • 110
  • [ 623-00-7 ]
  • [ 141-97-9 ]
  • [ 1528-41-2 ]
  • [ 86369-43-9 ]
Reference: [1] Tetrahedron Letters, 2007, vol. 48, # 18, p. 3289 - 3293
  • 111
  • [ 623-00-7 ]
  • [ 141-97-9 ]
  • [ 1528-41-2 ]
Reference: [1] Tetrahedron, 1982, vol. 38, # 23, p. 3479 - 3483
  • 112
  • [ 141-97-9 ]
  • [ 933-88-0 ]
  • [ 51725-82-7 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 2005, vol. 53, # 24, p. 9566 - 9570
[2] Chemische Berichte, 1935, vol. 68, p. 227,230
[3] Diss. &lt;T. H. Berlin 1932&gt; S. 60,
  • 113
  • [ 141-97-9 ]
  • [ 88-73-3 ]
  • [ 31912-02-4 ]
Reference: [1] Journal of Organic Chemistry, 1973, vol. 38, p. 3004 - 3011
  • 114
  • [ 141-97-9 ]
  • [ 32933-03-2 ]
YieldReaction ConditionsOperation in experiment
71% With potassium carbonate In ethyl acetate at 20℃; for 1.5 h; General procedure: Powdered K2CO3(207 mg, 1.5 mmol) and 1,3-cyclohexanedione (8a) (56 mg, 0.50 mmol) were added to a suspension of sulfonium salt 13(332 mg, 0.75 mmol) in EtOAc (5 mL). After stirring at r.t. for 1.5 h, the reaction was quenched with water (10 mL) and the whole mixture was extracted with EtOAc (2×10 mL). The combined organic layer was washed with brine (10 mL) and dried over anhydrous MgSO4. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography (silica gel, 30percent EtOAc in hexane) to provide 1a (60 mg, 87percent) as a colorless oil
Reference: [1] Chemical and Pharmaceutical Bulletin, 2016, vol. 64, # 12, p. 1763 - 1768
  • 115
  • [ 141-97-9 ]
  • [ 106-93-4 ]
  • [ 32933-03-2 ]
YieldReaction ConditionsOperation in experiment
60% With potassium carbonate In acetone Step 1) ethyl 1-acetylcyclopropanecarboxylate
To a solution of ethyl 3-oxobutanoate (26 g, 200 mmol) in acetone (500 mL) was added potassium carbonate (82.8 g, 600 mmol) followed by 1,2-dibromoethane (45.12 g, 240 mmol).
The reaction was refluxed for 24 hrs, the reaction mixture was then filtered.
The filtrate was concentrated in vacuo, and the residue was purified by a silica gel column chromatography (1:50(v/v) EtOAc/n-hexane) to afford the title compound as colorless oil (18.7 g, 60percent).
MS (ESI, pos. ion) m/z: 157 (M+1);
1H NMR (400 MHz, CDCl3): δ 1.25-1.29 (t, J=7.2 Hz, 3H), 1.45 (s, 4H), 2.45 (s, 3H), 4.18-4.20 (q, 2H).
60% With potassium carbonate In acetone for 24 h; Reflux To a solution of ethyl 3-oxobutanoate (26 g, 200 mmol) in acetone (500 mL) was added potassium carbonate (82.8 g, 600 mmol) followed by 1,2-dibromoethane (45.12 g, 240 mmol).
The reaction was refluxed for 24 hrs, the reaction mixture was then filtered.
The filtrate was concentrated in vacuo, and the residue was purified by a silica gel column chromatography (1:50(v/v) EtOAc/n-hexane) to afford the title compound as colorless oil (18.7 g, 60 percent).
MS (ESI, pos. ion) m/z: 157 (M+1);
1H NMR (400MHz, CDCl3): δ 1.25 - 1.29 (t, J=7.2 Hz, 3H), 1.45 (s, 4H), 2.45 (s, 3H), 4.18 - 4.20 (q, 2H).
60% With potassium carbonate In acetone for 24 h; Reflux; Inert atmosphere To a solution of ethyl 3-oxobutanoate (26 g, 200 mmol) in acetone (500 mL) was added potassium carbonate (82.8 g, 600 mmol) followed by 1 ,2-dibromoethane (45.12 g, 240 mmol). The reaction was refluxed for 24 hrs, then the reaction mixture was filtered. The filtrate was concentrated in vacuo, and the residue was purified by a silica gel column chromatography (l :50(v/v)EtOAc/n-hexane) to afford the title compound as colorless oil (18.7 g, 60 percent).MS (ESI, pos. ion) m/z: 157 (M+l);1H NMR (400MHz, CDCl3): δ 1.25 - 1.29 (t, J=7.2 Hz, 3H), 1.45 (s, 4H), 2.45 (s, 3H),4.18 - 4.20 (q, 2H).
52% With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 48 h; Part A: Ethyl 1-acetylcyclopropanecarboxylate. To a stirred solution of ethyl 3-oxobutanoate (10 mL, 78.45 mmol) and 1 ,2- dibromoethane (6.5 mL, 78.45 mmol) in 150 mL of DMF was added potassium carbonate (22.7 g, 164.74 mmol). The resulting reaction mixture was stirred at room temperature for 2 days. The solution was diluted with 300 mL of water. The product was extracted into diethyl ether (2 x 200 mL), and the combined organic extracts were washed with water (1 x 1000 mL), and dried (MgSO4). Filtration and atmospheric distillation of the ether provided the crude product, which was distilled under reduced pressure (10 mBar) to provide ethyl 1-acetylcyclopropanecarboxylate (6.4273 g, 52percent). LCMS: (M+H) +: not detected. Part A: Ethyl 1 -acetylcyclopropanecarboxylateTo a solution of ethyl 3-oxobutanoate (10.0 g, 76.84 mmol) in DMF (150 mL) was added potassium carbonate (22.30 g, 161.3 mmol) and 1 ,2-dibromoethane (6.62 mL, 76.82 mmol). The mixture was stirred for 2 days, and then filtered. The solution was diluted with water (300 mL), and extracted with Et2O (2 x 200 mL). The combined organic phase was washed with a fresh portion of water (100 mL), dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was subjected to vacuum distillation at ca. 10 mbar, and the fraction boiling at 100 0C was collected to give ethyl 1- acetylcyclopropanecarboxylate (7.6482 g, 64percent) as a colorless oil.
51% at 20℃; Step 1 : ethyl 1-acetylcyclopropanecarboxylateA mixture of ethyl 3-oxobutanoate (100 g, 0.769 mol), 1 , 2-dibromoethane (215.7 g, 1.153 mol) and K2CO3 (424 g, 3.07 mol) was stirred at room temperature overnight. Water (800 mL) was added and the reaction mixture was extracted with ether (3 X 500 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, concentrated in vacuo, and the residue was purified by column chromatography to give the title compound as a light yellow oil (51 g, 51 percent): 1H NMR (400 MHz, CDCI3) δ 4.10-4.16 (m, 3H), 2.40 (s, 2H), 1.39 (s, 3H), 1.18-1.24 (m, 4H); ES-LCMS m/z 157 (M+H)+.
50% With potassium carbonate In dimethyl sulfoxide at 25℃; for 24 h; Inert atmosphere The ethyl-3-oxobutanoate (10.0g, 76.8mmol) and 1,2-dibromoethane (21.7g, 115mmol) was dissolved in dimethyl sulfoxide (300mL), under nitrogen gas protection, and then was added portionwise potassium carbonate (42.5g, 307mmol).The reaction mixture was stirred for 24 hours at 25 °C. Adding water (10 ml) quenching the reaction, is filtered to remove insoluble matter, the filtrate is extracted with ethyl acetate (20mLx3). Combining the organic phase, dried with anhydrous sodium sulfate, filtered, concentrated filtrate under reduced pressure,purification by silica gel column chromatography (10: 1 petroleum ether / ethyl acetate, Rf = 0.4) to give ethyl 1-acetylcyclopropanoate (6.00 g, white oil). Yield: 50percent.
0.6 g With potassium carbonate In dimethyl sulfoxide at 20℃; for 48 h; To a stirred solution of ethyl 3-oxobutanoate (1 g, 7.68 mmol) in DMSO (10 mL) was added K2CO3(3.19 g, 23.05 mmol) at RT followed by drop-wise addition of 1, 2 dibromo ethane (3.61 g, 19.2 mmol). The reaction mixture was stirred at ambient temperature for 48 h and quenched with water (50 mL). The reaction mixture was extracted with EtOAc (200 mL), washed with brine (50 mL), dried over Na2S04, filtered and evaporated under reduced pressure. The crude was purified flash chromatography (Silica gel 230-400, 2percent EtOAc/petroleum ether) to give ketoester B-20a (0.6 g).XH NMR (CDC13, δ = 7.26 ppm, 400 MHz): 4.20 (q, d = 7.2, 2 H), 2.46 (s, 3 H), 1.46 (s, 4 H), 1.28 (t, J = 7.2, 3 H).
13 g With potassium carbonate In N,N-dimethyl-formamide 13.0 g of ethyl acetoacetate was added to a 250 mL reaction flask. Then, added sequentially 130 mL of DMF, 37.6 g of 1,2-dibromoethane, 52.44 g of potassium carbonate. Stirring, reaction overnight. Was added to 650 mL of water. Ethyl acetate extraction. Dry. Concentration of the distillation yielded 13.0 g of compound 1.
152 g With potassium carbonate In N,N-dimethyl-formamide at 35℃; Ethylacetoacetate (130.2 g, 1.0 mol) was dissolved in DMF (400 mL)Anhydrous potassium carbonate (276.5 g, 2. Ommo 1), 1,2-dibromoethane (338 g, 1.8 mol) was added, heated to 35 ° C, and mechanically stirred overnight.The solvent was evaporated under reduced pressure to give ethyl 1-acetylcyclopropanecarboxylate (crude 152 g, 97percent)

Reference: [1] Tetrahedron Letters, 2005, vol. 46, # 4, p. 635 - 638
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 2, p. 420 - 422
[3] Tetrahedron Asymmetry, 2010, vol. 21, # 5, p. 631 - 635
[4] Journal of Organic Chemistry, 2011, vol. 76, # 8, p. 2807 - 2813
[5] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1983, vol. 19, # 6, p. 644 - 650[6] Khimiya Geterotsiklicheskikh Soedinenii, 1983, vol. 19, # 6, p. 801 - 807
[7] European Journal of Organic Chemistry, 2005, # 19, p. 4167 - 4178
[8] Synlett, 2009, # 13, p. 2177 - 2179
[9] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 839 - 862
[10] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1988, vol. 27, p. 530 - 536
[11] Patent: US2010/239576, 2010, A1,
[12] Patent: EP2408300, 2016, B1, . Location in patent: Paragraph 0368
[13] Patent: WO2010/45095, 2010, A1, . Location in patent: Page/Page column 88
[14] Patent: WO2009/61879, 2009, A1, . Location in patent: Page/Page column 165, 177
[15] Patent: WO2010/141545, 2010, A1, . Location in patent: Page/Page column 24-25
[16] Patent: CN105566324, 2016, A, . Location in patent: Paragraph 0099; 0100; 0101; 0102
[17] Journal of the Chemical Society, 1885, vol. 47, p. 814[18] Chemische Berichte, 1884, vol. 17, p. 324
[19] Journal of the Chemical Society, 1887, vol. 51, p. 829
[20] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1925, vol. 145, p. 61[21] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1927, vol. 172, p. 234
[22] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 10, p. 3187 - 3194
[23] Russian Chemical Bulletin, 1994, vol. 43, # 1, p. 84 - 88[24] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1994, # 1, p. 89 - 93
[25] Patent: US5194431, 1993, A,
[26] Patent: US5286723, 1994, A,
[27] Patent: WO2015/5901, 2015, A1, . Location in patent: Page/Page column 638
[28] Patent: CN105906545, 2016, A, . Location in patent: Paragraph 0048; 0049
[29] Patent: CN104557871, 2017, B, . Location in patent: Paragraph 0143-0145
  • 116
  • [ 141-97-9 ]
  • [ 107-06-2 ]
  • [ 32933-03-2 ]
Reference: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1990, vol. 39, # 3.2, p. 631 - 633[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1990, # 3, p. 710 - 712
[3] Russian Chemical Bulletin, 1994, vol. 43, # 1, p. 84 - 88[4] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1994, # 1, p. 89 - 93
[5] Patent: US2003/65212, 2003, A1,
  • 117
  • [ 64648-13-1 ]
  • [ 141-97-9 ]
  • [ 32933-03-2 ]
Reference: [1] Organic Preparations and Procedures International, 1992, vol. 24, # 5, p. 548 - 552
  • 118
  • [ 141-97-9 ]
  • [ 106-93-4 ]
  • [ 32933-03-2 ]
Reference: [1] Patent: US5587386, 1996, A,
  • 119
  • [ 141-97-9 ]
  • [ 106-93-4 ]
  • [ 32933-03-2 ]
YieldReaction ConditionsOperation in experiment
65.1% With potassium carbonate In acetone Referential Example 11-1
Ethyl 1-acetylcyclopropanecarboxylate
Ethyl acetoacetate (100 g, 0.77 mol) was dissolved in acetone (500 ml).
To the thus obtained solution was added dibromoethane (361 g, 1.92 mol) and potassium carbonate (266 g, 1.92 mol) and the mixture was heated under reflux for 4 days.
After filtering off insoluble matter, the filtrate was distilled under reduced pressure (80° C./8 mmHg) to obtain 78.1 g (65.1percent) of the title compound as a colorless oily substance.
1 H-NMR (400 MHz, CDCl3) δ: 1.29 (3H, t, J=7.33 Hz), 1.47 (4H, s), 2.47 (3H, s), 4.21 (2H, q, J=7.33 Hz).
Reference: [1] Patent: US6121285, 2000, A,
  • 120
  • [ 141-97-9 ]
  • [ 106-93-4 ]
  • [ 2986-03-0 ]
  • [ 32933-03-2 ]
Reference: [1] Journal of Organic Chemistry USSR (English Translation), 1983, vol. 19, p. 474 - 480[2] Zhurnal Organicheskoi Khimii, 1983, vol. 19, # 3, p. 541 - 548
  • 121
  • [ 56692-06-9 ]
  • [ 141-97-9 ]
  • [ 32933-03-2 ]
Reference: [1] Organic Preparations and Procedures International, 1992, vol. 24, # 5, p. 548 - 552
  • 122
  • [ 14668-82-7 ]
  • [ 141-97-9 ]
  • [ 32933-03-2 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1972, vol. 45, p. 1884 - 1888
  • 123
  • [ 141-97-9 ]
  • [ 106-93-4 ]
  • [ 75-21-8 ]
  • [ 32933-03-2 ]
  • [ 107-21-1 ]
Reference: [1] Chemistry Letters, 1987, p. 2235 - 2238
  • 124
  • [ 141-97-9 ]
  • [ 6307-04-6 ]
  • [ 32933-03-2 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1973, p. 65 - 68
  • 125
  • [ 645-00-1 ]
  • [ 141-97-9 ]
  • [ 14318-64-0 ]
YieldReaction ConditionsOperation in experiment
86% With caesium carbonate In 1,4-dioxane at 100℃; for 12 h; General procedure: A mixture of aryl iodide (5 mmol), ethyl acetoacetate(7.5 mmol), Cu2+/4A (0.5 g, 0.1 mol percent copper) and Cs2CO3 (12.5 mmol) indioxane (10 ml) was stirred at 100 C for 12 h. The solid was filtered and thefiltrate was evaporated in vacuo. The products were purified by columnchromatography (silica gel, hexane/acetone 4:1 eluent). The products werecharacterized by 1H NMR and GC–MS.
Reference: [1] Tetrahedron Letters, 2015, vol. 56, # 46, p. 6389 - 6392
  • 126
  • [ 141-97-9 ]
  • [ 459-57-4 ]
  • [ 3449-63-6 ]
Reference: [1] Journal of the American Chemical Society, 2018, vol. 140, # 38, p. 11916 - 11920
[2] Journal of Medicinal Chemistry, 1995, vol. 38, # 11, p. 1998 - 2008
[3] Tetrahedron Asymmetry, 2005, vol. 16, # 14, p. 2475 - 2485
[4] Patent: US2012/46307, 2012, A1, . Location in patent: Page/Page column 34
  • 127
  • [ 141-97-9 ]
  • [ 17790-74-8 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 2010, vol. 58, # 8, p. 4977 - 4982
  • 128
  • [ 2101-88-4 ]
  • [ 141-97-9 ]
  • [ 20725-34-2 ]
Reference: [1] Journal of Chemical Crystallography, 2009, vol. 39, # 1, p. 32 - 35
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 3, p. 380 - 383
[3] Journal of the Chinese Chemical Society, 2005, vol. 52, # 1, p. 103 - 108
[4] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 4, p. 781 - 786
[5] Indian Journal of Heterocyclic Chemistry, 2012, vol. 22, # 1, p. 81 - 84
[6] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2016, vol. 55B, # 5, p. 590 - 597
  • 129
  • [ 41995-04-4 ]
  • [ 141-97-9 ]
  • [ 23082-51-1 ]
Reference: [1] Journal of the Chemical Society, 1947, p. 232,236
  • 130
  • [ 141-97-9 ]
  • [ 22921-68-2 ]
  • [ 19725-82-7 ]
Reference: [1] Patent: WO2006/67444, 2006, A1, . Location in patent: Page/Page column 64-65
  • 131
  • [ 141-97-9 ]
  • [ 20207-16-3 ]
Reference: [1] Patent: WO2013/67578, 2013, A1, . Location in patent: Page/Page column 96; 97
[2] Chemical and Pharmaceutical Bulletin, 2013, vol. 61, # 12, p. 1248 - 1263
[3] Patent: WO2015/20930, 2015, A1,
[4] Patent: WO2018/96159, 2018, A1,
  • 132
  • [ 141-97-9 ]
  • [ 101667-98-5 ]
Reference: [1] Patent: WO2015/136556, 2015, A2,
[2] Patent: WO2015/136557, 2015, A2,
[3] European Journal of Medicinal Chemistry, 2016, vol. 115, p. 148 - 160
[4] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 9, p. 1663 - 1669
  • 133
  • [ 141-97-9 ]
  • [ 24241-18-7 ]
  • [ 125208-06-2 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1989, # 4, p. 467 - 471
  • 134
  • [ 141-97-9 ]
  • [ 100-83-4 ]
  • [ 17356-08-0 ]
  • [ 329689-23-8 ]
YieldReaction ConditionsOperation in experiment
96% With sodium hydrogensulfate monohydrate In hexane; acetonitrile for 0.5 h; Reflux; Sonication; Green chemistry General procedure: To a solution of an aldehyde (1 mmol), ethyl/methyl acetoacetate or acetylacetone(1 mmol) and urea/thiourea (1.2 mmol) in n-hexane/CH3CN (2.5:0.5 mL), NaHSO4·H2O(3 mmol) was added. The reaction mixture was then heated to reflux and synchronously irradiated by ultrasound (240 W) via a micro-tip probe for an appropriate time. Progress of the reactions was monitored by TLC (n-hexane/EtOAc: 5/3). After completion of the reaction, the solution was cooled to room temperature and H2O (5 mL) was then added followed by stirring for 5 min. The mixture was extracted with EtOAc (3 × 8 mL) anddried over anhydrous Na2SO4. Evaporation of the solvent and recrystallization of the crude product in hot MeOH affords the pure DHPM (4–69) in 91–98percent yield (Tables 2 and 3).
96% With alumina In neat (no solvent) at 100℃; for 0.15 h; Microwave irradiation; Green chemistry General procedure: A mixture of the aldehyde 1 (2 mmol), the 1,3-dicarbonyl compound 2 (2 mmol), the corresponding urea derivative 3(3 mmol) and the 3D printed Al2O3 structure (0.350 g) was submitted to microwave irradiation (100 °C) in coated vial. After completion of the reaction, as indicated by TLC, the mixture was cooled and the desired compound solidified. For those 1,2,3,4-tetrahydropyrimidine-5-carboxylates that not solidified, the reaction mixture was poured onto crushed ice and stirred for 5-10 min. The solid obtained was filtered under suction, washed with ice-cold water (20 mL) and then purified by column chro-matography or recrystallization from the appropriate solvent.
94% With Graphite In neat (no solvent) at 120℃; for 0.166667 h; Green chemistry General procedure: A mixture of benzaldehyde (106mg, 1mmol), urea (60mg, 1mmol), ethylacetoacetate (130mg, 1mmol) and (10mg, 10percentw/w) graphite was heated at 70°C (120°C in case of thiourea). The heterogenous mixture slowly became clear and a solid product started to seperate out. After completion of the reaction (1h, TLC) the entire mass solidified. The solid mass was crushed, washed with 5mL of cold water to remove unreacted urea and filtered.The solid was then dissolved in hot ethanol, and the catalyst was separated by filtration. On cooling the filtrate pure crystals of the product (1a) was obtained, yield 97percent (237mg). In all the cases, the product obtained was characterized by comparing spectral data and melting points with literature data.
90% With o-phthalimide-N-sulfonic acid In neat (no solvent) at 120℃; for 3 h; General procedure: To a mixture of aryl aldehyde 4 (1 mmol), β-dicarbonyl 5 (1 mmol), and urea or thiourea 6 (1.2 mmol) was added 10 mol percent of phthalimide-N-sulfonic acid (PISA). The reaction mixture was heated to 120 °C on a heating mantle for the appropriate time. After completion of the reaction, as indicated by TLC analysis, the system was cooled to room temperature. Ethanol (5 mL) was added to the reaction mixture, and the mixture was heated until a homogeneous solution was obtained. Next, ethyl acetate was added to the resulting mixture and then cooled to RT, and the catalyst was recovered by filtration and washed thoroughly with ethyl acetate and then diethyl ether. The recovered catalyst was then reused under the same conditions as above for at least five reactions. After this, the organic phase was concentrated by evaporation, distilled water was added to the residue, and the solid thus obtained.The resulting solid product was filtered off, washed with cold water, and then thereaction mixture was subjected to isolation with preparative TLC using a mixture of ethyl acetate and n-hexane (3:10) as eluent.
90% at 120℃; for 3 h; Green chemistry General procedure: A mixture of aryl aldehyde 1 (1 mmol), b-dicarbonyl 2 (1 mmol), urea or thiourea 3 (1.2 mmol), and 10 mol percent of PPI was added and the reaction mixture was heated at 120 C for 1–3 h. During the heating, the progress of the reaction mixture was monitored by TLC analysis. After completion of the reaction, the reaction was cooled to room temperature. The solid product was dissolved in ethanol and water, filtered by simple filtration, and washed with water (5 mL), and the residue was recrystallized from ethanol to give the desired compounds in high yields. The filtrate was evaporated to remove water and leave the catalyst. The same catalyst was employed to synthesize further derivatives. The products are known and their identity was confirmed by comparison of their physical and spectroscopic data with those available in the literature.
88% With tris(pentafluorophenyl)borate In ethanol for 3 h; Reflux; Green chemistry General procedure: A mixture of benzaldehyde 1a (106 mg, 1 mmol), ethyl acetoacetate 2a (130 mg, 1 mmol) and urea 3a (90 mg,1.5 mmol) in EtOH (10 mL) was refluxed in the presence of B(C6F5)3 (18.1 mg, 1 molpercent). After completion of reaction, as indicated by TLC analysis, the solvent was evaporated. The resulting mass was treated with ice-cold water and the solid obtained was filtered, washed with cold water, dried and re-crystallized from ethanol to give pure product (4a).
87% With molybdophosphoric acid supported on Y zeolite In acetonitrile for 7 h; Reflux Method A. A mixture of 1 (122 mg, 1.0 mmol), ethylacetoacetate (130 mg, 1.0 mmol), and thiourea (190 mg,2.5 mmol) in MeCN (15 ml) was mixed with HPA supportedon Y zeolite (8 wtpercent NaY + 0.5 mM HPA) and refluxed for7 h. After cooling, the heteropoly acid (HPA) supported onHY filtered off and washed with hot water and ethanol toremove thiourea from the surface of the catalyst. Then, thecatalyst dried and was maintained for new runs. The filtratewas evaporated to dryness and the residue was recrystallized from EtOH to afford 2 (254 mg, 87 percent), m.p. 181–185 °C (Lit.[6, 7] 184–186 °C), Rf = 0.71. 1H NMR (DMSO-d6): δ 10.29(s, 1 H, NH), 9.60 (s, 1 H, NH), 9.44 (s, 1 H, OH), 7.10 (t,J = 7.8 Hz, H-5), 6.65 (d, 1 H, J2’,4′ = 2.4Hz, Harom.-2′), 6.64(m, 2 H, Harom.-4 + Harom.-6), 5.09 (d, 1 H, JNH,4 = 5.5 Hz,H-4), 4.02 (q, 2 H, J = 7.8Hz, CH2CH3), 2.28 (s, 3 H, C6-Me),1.12 (t, 3 H, J = 7.8 Hz, CH2CH3). 13C NMR (DMSO-d6): δ174.6 (C = S), 165.7 (CO2Et), 157.9 (C-6), 145.3 (C3’-OH + Carom.-1′), 130.0 (Carom.-5′), 117.7 (Carom.-2′ +Carom.-6′), 133.6 Carom.-4′), 101.2 (C-5), 60.1 (CH2CH3),54.5 (C-4), 17.7, 17.6 (C6-Me), 14.5 (CH2CH3). EI-MS:m/z (percent) = 292 [M]+. Anal. Calcd. for C14H16N2O3S(292.35): C, 57.52; H, 5.52; N, 9.58. Found: C, 57.32;H, 5.39; N, 9.32 percent. Method B. A mixture of 1 (244 mg, 2.0 mmol), ethylacetoacetate (300 mg, 2.30 mmol), and thiourea (380 mg,5.0 mmol) in EtOH (15 ml) in the presence conc. Hydrochloricacid (1 ml) was heated under reflux for 3 h. After cooling,the mixture was poured onto ice (20 g). The precipitate wasfiltered and dried and recrystallized from EtOH to give 2(292 mg, 50 percent), TheNMR spectra, m.p. and mixed m.p. werealmost similar for those of 2 prepared in method A.
86% for 4 h; Reflux General procedure: A mixture of 0.025 mol of urea or thiourea, 0.025 mol of an arylaldehyde, 0.025 mol of ethyl acetoacetate or acetylacetone, 10 mL ethanol and 3 drops of a liquid or 2-3 mg of solid phenol was heated under reflux for 6-24 h and the reaction mixture was then cooled to 0 °C and the product was filtered, washed with water, dried and recrystallized from a suitable solvent. The progress of the reaction was monitored by TLC using ethyl acetate and n-hexane (1:2) as eluent.
85% With chloro-trimethyl-silane In acetonitrile for 24 h; Inert atmosphere; Reflux General procedure: A 10 mmol mixture of the corresponding benzaldehyde (4),15 mmol of methyl or ethyl acetoacetate (5), 761 mg (10 mmol,1.0 equiv) of thiourea (6), 1.27 mL (10 mmol, 1.0 equiv) oftrimethylsilylchloride (TMSCl) and 7.0 mL of anhydrous acetonitrileunder nitrogen atmosphere was formulated in a 50 mL roundbottom flask, equipped with a magnetic stirring bar. The watercondenser was set at the neck of round bottom flask then the mixturewas stirred for 1 min at room temperature to allow homogenization,followed by reflux for 24 h at oil bath. After cooling thereaction mixture, solvent was evaporated under reduced pressurethrough rotary evaporator. Thereafter, 500 mL of ice water waspoured into reaction mixture and allowed to stir for 1 h in orderto obtain maximum precipitation. Filtration delivered the pureDHPMs. Where needed, the product was recrystallized or directlypurified by gradient dry flash chromatography using appropriatesolvents. The physical and spectroscopic data of DHPM 7–12 werefound in good agreement with the literature [11,13,20]. 4.2.1.1.
83% With psychortria douarrei catalyst dispersed on montmorillonite K10 In neat (no solvent) at 80℃; for 1.2 h; A mixture of ethyl acetoacetate (781 mg, 6.Ommol),3-hydrobenzaldehyde (488 mg, 4.0 mmol), thiourea (457 mg,6.0 mmol) and P douarrei crude catalyst (265 mg, amount corresponding to 1.0 mmol of nickel following previous dosing), supported on montmorillonite K10 (265 mg) was placed in a 10 mE sealed tube. The tube was heated to 80° C. in oil bath, under magnetic stirring for 1.2 h. The mixture was then extracted with hot ethanol (10 mE, 70° C.) and filtered in order to remove the catalyst, which was reactivated by heating (150°C.). The solutionwas poured into crushed ice (20 g) and stirred for 20 mm. The solid separated was filtered under suction, washed with cold water (30 mE) and recrystallized from hot ethanol, affording pure product, as colorless crystals (973 mg, 83percent). The same procedure was followed with G. pruinosa catalyst and commercial NiCl2. Mp 185-186° C. (184-186°C.);IR 3298,3181,3115,2982, 1663, 1617, 1573 cm’; ‘H NMR (DMSO-d5, 300 MHz) ö: 1.14 (t, J=7.4 Hz, 3H), 2.29 (s, 3H), 4.04 (q, J=7.4 Hz, 2H), 5.11 (d, J=3.5 Hz, 1H), 6.60-6.71 (m, 3H), 7.06-7.15 (m, 1H), 9.42 (brs, 1H),9.62 (brs, 1H), 10.29 (brs, 1H); ‘3C NMR (DMSO-d5, 75 MHz) ö: 14.0, 17.1, 54.2, 59.6, 100.8, 113.0, 114.4, 117.0, 129.3, 144.8, 144.9, 157.4, 165.4, 174.2. MS (EI+) calculated for C,4H,6N2035 [M]292.1. found 293.1 [M+H].
80% With bis(p-sulfoanilino)triazine-functionalized silica-coated magnetite nanoparticles In neat (no solvent) at 100℃; for 1.16667 h; General procedure: A mixture of aromatic aldehyde (1 mmol), b-keto ester or dimedone (1 mmol) and urea or thiourea (1.2 mmol) was stirred in presence MNPs-BSAT (20 mg) at 100 °C under solvent-free condition for the appropriate time (Scheme 1). After completion of the reaction as indicated by TLC (using n-hexane-ethyl acetate as eluent), the resulting mixture was diluted with hot ethanol (15 mL) and the catalyst separated by an external magnet and washed with hot ethanol (5 mL) two times. The filtrate was cooled to room temperature and the crude products which precipitated were collected and recrystallized from ethanol if necessary.
79% With tin(II) chloride dihdyrate In acetonitrile at 70 - 75℃; Sonication General procedure: A mixture of an aldehyde (10 mmol), a diamino compound (12 mmol), a dicarbonyl compound (10 mmol, mL), SnCl2·2H2O (10 molpercent) and acetonitrile (10 mL) was mixed in a pyrex tube. The mixture was then irradiated in ultrasonic bath at 70–75 °C. The reaction was monitored by TLC. After the completion of the reaction, the resulting precipitate was filtered and crude product was recrystallized from an appropriate solvent or purified through columnchromatography.
75% With ytterbium(III) triflate In acetonitrile at 120℃; for 1 h; Microwave irradiation General procedure: The appropriate β-keto ester (0.75–3.0mmol, 1.5 equiv.), the appropriate aldehyde (0.5–2.0mmol, 1 equiv.), the appropriate urea or thiourea (0.5–2.0mmol, 1 equiv.) and Yb(OTf)3 (0.05–0.20mmol, 0.10 equiv.) were placed in a microwave oven vial (0.5–2.0mL) with a magnetic stirring bar and dissolved in THF or MeCN (0.5–1.0mL). The resulting mixture is heated to 120°C for 30–60min using microwave irradiation. The resulting mixture is poured onto an ice-water mixture and left for precipitation. The resulting crude solids were purified by recrystallization, DCVC or flash chromatography.
74% With copper dichloride In ethanol at 80℃; for 4 h; General procedure: To a stirred mixture of thiourea (1.00 mmol), substituted benzaldehydes E–G (Scheme 1)(1.00 mmol), ethyl acetoacetate (130 mg, 1.00 mmol), and anhydrous cupric chloride(10 molpercent) were added. The mixture was heated at 80°C for 4 h under stirring. After thereaction was completed (checked by TLC), a mixture of H2O:EtOH 8:5 (13 mL) was added andthe resulting slurry was stirred at 80°C until total dissolution. After being cooled to roomtemperature, the reaction mixture was poured onto crushed ice (30 g) and stirred for5–10 min. The separated solid was filtered under suction (water aspirator), washed withice-cold water (50 mL), and then recrystallized from hot ethanol to afford the pureproduct.2.3. Ethyl-4-(3-hydroxyphenyl)-6-methyl-2-thioxo-pyrimidine-5-carboxylate(monastrol) L1))From 3-hydroxybenzaldehyde (E) (122 mg). Yield: 216 mg (74percent); mp 185–186°C (Lit. [23, 25]184–186°C).
72% With 1-butyl-1,2,4-triazolium triflate In ethanol at 80℃; for 1 h; Green chemistry General procedure: Catalyst 1a-c (10 molpercent) was added to a solution of aldehyde (1.0 mmol), β-ketoester (1.5 mmol) and urea or thiourea (2.0 mmol) in ethanol (0.5 mL). The reaction mixture was heated at 80 °C using oil bath for the specified time (0–5 h). The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to room temperature and subsequently quenched with a mixture of water:ethanol (5:0.5 mL). The solid product was filtered and washed with n-hexane (5mL ×2), which afforded pure 3,4-dihydropyrimidin-2(1H)-ones or 3,4-dihydropyrimidin-2(1H)-thiones in pure form.
71% at 100℃; for 3 h; General procedure: Aldehyde (3 mmol), ethyl acetoacetate (0.586 g, 4.5 mmol), urea (0.270 g, 4.5 mmol) or thiourea (0.343 g, 4.5 mmol), and β-cyclodextrin (17 mg, 0.5 molpercent) were mixed in a 25 mL round bottom flask for 3h at a temperature of 100 °C. The reaction mixture was cooled and the solid was solubilized in ethanol and the addition of few drops of cold water to precipitate the product. The precipitated solid was filtered on sintered funnel. The crude product was further purified by recrystallization from ethanol to afford pure 3,4-dihydropyrimidin-2(1H)-ones. After separation of the product by filtration, the filtrate was washed with ethyl acetate and the aqueous phase was concentrated on rotary evaporator obtaining the catalyst.
64% With 1-ethyl-1,2,4-triazolium phenylsulfonate In ethanol at 70 - 80℃; for 2.5 h; General procedure: Catalyst 1-ethyl-1,2,4-triazolium phenylsulfonate (TrHEtPS) (10 mol) was added to a solution of urea or thiourea (2.0 mmol), β-ketoester (1.5 mmol) and aldehyde (1.0 mmol) in ethanol (0.5 mL). The reaction mixture was heated at 70 to 80 °C for the specified time (0-5 h) (Scheme-II). The completion of the reaction was monitored by thin layer chromatography (ethyl acetate:hexane: :4:1) and then the reaction mixture was cooled to room temperature. Then, quenched with mixture of water: ethanol (5:0.5 mL). The obtained solid product was filtered, and washed with n-hexane (5mL) and afforded 3,4-dihydropyrimidin-2(1H)-ones or 3,4-dihydropyrimidin-2(1H)-thiones.
52% With 25,26,27,28-terahydroxycalix[4]arene-5,11,7,23-tetrasulfonic acid In ethanol for 8 h; Reflux General procedure: Aldehydes (3 mmol), ethyl acetoacetate (4.5 mmol) and (thio)urea (4.5 mmol) were dissolved in 3 mL of ethanol containing p-sulfonic acid calix[4]arene (0.5 mol percent). The mixture was heated under reflux and stirred for 8 h.20 All DHPMs were characterized by NMR (1H and 13C), infrared, melting point and elemental analysis. Characterization data for compounds BA9, BA11-BA14, BA16-BA21, BA24-BA28, BA30 and BA32 were recently reported by da Silva et al.20 Data for compounds BA2, BA10, BA15, BA22, BA29, BA31 and BA33 are listed as Supplementary data.

Reference: [1] Synthetic Communications, 2007, vol. 37, # 22, p. 3907 - 3916
[2] ACS Catalysis, 2013, vol. 3, # 7, p. 1420 - 1430
[3] Molecules, 2006, vol. 11, # 8, p. 649 - 654
[4] Phosphorus, Sulfur and Silicon and the Related Elements, 2009, vol. 184, # 9, p. 2465 - 2471
[5] Synthetic Communications, 2013, vol. 43, # 11, p. 1477 - 1483
[6] Phosphorus, Sulfur and Silicon and the Related Elements, 2013, vol. 188, # 11, p. 1634 - 1642
[7] Applied Catalysis A: General, 2017, vol. 530, p. 203 - 210
[8] Tetrahedron Letters, 2002, vol. 43, # 34, p. 5913 - 5916
[9] Synlett, 2004, # 2, p. 279 - 282
[10] Phosphorus, Sulfur and Silicon and the Related Elements, 2012, vol. 187, # 4, p. 544 - 553
[11] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 4, p. 823 - 826
[12] Heterocyclic Communications, 2006, vol. 12, # 1, p. 61 - 66
[13] Synthetic Communications, 2009, vol. 39, # 5, p. 880 - 886
[14] Beilstein Journal of Organic Chemistry, 2009, vol. 5,
[15] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 13, p. 2897 - 2899
[16] Phosphorus, Sulfur and Silicon and the Related Elements, 2009, vol. 184, # 7, p. 1722 - 1728
[17] Chemistry - A European Journal, 2013, vol. 19, # 13, p. 4156 - 4168
[18] Tetrahedron Letters, 2003, vol. 44, # 14, p. 2889 - 2891
[19] Journal of Heterocyclic Chemistry, 2007, vol. 44, # 4, p. 979 - 981
[20] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2007, vol. 46, # 11, p. 1886 - 1889
[21] Asian Journal of Chemistry, 2011, vol. 23, # 9, p. 3993 - 3995
[22] RSC Advances, 2015, vol. 5, # 60, p. 48506 - 48515
[23] RSC Advances, 2014, vol. 4, # 67, p. 35559 - 35567
[24] Heterocycles, 2003, vol. 60, # 11, p. 2435 - 2440
[25] Heterocycles, 2006, vol. 68, # 6, p. 1217 - 1224
[26] Journal of Heterocyclic Chemistry, 2007, vol. 44, # 1, p. 211 - 214
[27] Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 2008, vol. 63, # 2, p. 178 - 182
[28] Research on Chemical Intermediates, 2015, vol. 41, # 9, p. 6635 - 6648
[29] Research on Chemical Intermediates, 2015, vol. 41, # 8, p. 5177 - 5203
[30] Synthesis, 2005, # 11, p. 1748 - 1750
[31] Catalysis Communications, 2011, vol. 15, # 1, p. 123 - 126
[32] Synthetic Communications, 2013, vol. 43, # 1, p. 139 - 146
[33] New Journal of Chemistry, 2016, vol. 40, # 1, p. 838 - 843
[34] Journal of the Chinese Chemical Society, 2007, vol. 54, # 2, p. 263 - 266
[35] Bulletin of the Korean Chemical Society, 2010, vol. 31, # 2, p. 351 - 354
[36] Chinese Journal of Chemistry, 2010, vol. 28, # 3, p. 388 - 392
[37] Journal of the Brazilian Chemical Society, 2011, vol. 22, # 7, p. 1379 - 1388
[38] Journal of Chemical Sciences, 2015, vol. 127, # 6, p. 1047 - 1052
[39] Antiviral Research, 2012, vol. 95, # 2, p. 118 - 127
[40] Catalysis Letters, 2012, vol. 142, # 12, p. 1505 - 1511
[41] Journal of Fluorescence, 2016, vol. 26, # 1, p. 31 - 35
[42] Green Chemistry, 2011, vol. 13, # 4, p. 1009 - 1013
[43] Asian Journal of Chemistry, 2016, vol. 28, # 1, p. 23 - 26
[44] Synthesis, 2011, # 14, p. 2261 - 2267
[45] Asian Journal of Chemistry, 2012, vol. 24, # 5, p. 1906 - 1908
[46] Asian Journal of Chemistry, 2013, vol. 25, # 8, p. 4588 - 4590
[47] Bioorganic Chemistry, 2016, vol. 64, p. 85 - 96
[48] Bulletin of the Korean Chemical Society, 2011, vol. 32, # 2, p. 656 - 658
[49] RSC Advances, 2016, vol. 6, # 112, p. 110928 - 110934
[50] RSC Advances, 2013, vol. 3, # 44, p. 22340 - 22345
[51] ChemCatChem, 2014, vol. 6, # 12, p. 3455 - 3463
[52] Patent: US2015/376224, 2015, A1, . Location in patent: Paragraph 0643; 0660
[53] Tetrahedron, 2008, vol. 64, # 9, p. 2035 - 2041
[54] Tetrahedron, 2009, vol. 65, # 51, p. 10608 - 10611
[55] Journal of Heterocyclic Chemistry, 2010, vol. 47, # 1, p. 136 - 146
[56] Bioorganic Chemistry, 2006, vol. 34, # 4, p. 173 - 182
[57] Journal of Organic Chemistry, 2012, vol. 77, # 22, p. 10184 - 10193
[58] Research on Chemical Intermediates, 2018, vol. 44, # 7, p. 4083 - 4101
[59] Journal of Molecular Graphics and Modelling, 2013, vol. 43, p. 47 - 57
[60] Synthesis, 2004, # 13, p. 2091 - 2093
[61] European Journal of Medicinal Chemistry, 2017, vol. 138, p. 300 - 312
[62] Journal of Coordination Chemistry, 2017, vol. 70, # 12, p. 2061 - 2073
[63] Journal of Chemical Sciences, 2015, vol. 127, # 9, p. 1539 - 1545
[64] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 9, p. 2463 - 2466
[65] Tetrahedron, 2013, vol. 69, # 38, p. 8245 - 8249
[66] Amino Acids, 2013, vol. 44, # 3, p. 1031 - 1037
[67] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 15, p. 4679 - 4682
[68] Asian Journal of Chemistry, 2018, vol. 30, # 9, p. 1999 - 2002
[69] Tetrahedron, 2000, vol. 56, # 13, p. 1859 - 1862
[70] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 8, p. 2645 - 2650
[71] Asian Journal of Chemistry, 2010, vol. 22, # 4, p. 2518 - 2528
[72] RSC Advances, 2016, vol. 6, # 107, p. 105087 - 105093
[73] ChemMedChem, 2010, vol. 5, # 4, p. 567 - 574
[74] Synthetic Communications, 2011, vol. 41, # 15, p. 2200 - 2208
[75] ChemMedChem, 2013, vol. 8, # 8, p. 1345 - 1352
[76] Tetrahedron, 2014, vol. 70, # 45, p. 8582 - 8587
[77] European Journal of Medicinal Chemistry, 2016, vol. 115, p. 230 - 244
[78] ChemMedChem, 2017, vol. 12, # 13, p. 1022 - 1032
[79] MedChemComm, 2018, vol. 9, # 8, p. 1282 - 1288
  • 135
  • [ 37622-16-5 ]
  • [ 141-97-9 ]
  • [ 100-83-4 ]
  • [ 329689-23-8 ]
Reference: [1] Heterocycles, 2005, vol. 65, # 5, p. 1177 - 1181
  • 136
  • [ 141-97-9 ]
  • [ 329689-23-8 ]
Reference: [1] Patent: EP2769765, 2014, A1, . Location in patent: Page/Page column
  • 137
  • [ 141-97-9 ]
  • [ 148901-68-2 ]
  • [ 148901-69-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2001, vol. 9, # 10, p. 2727 - 2743
[2] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 20, p. 2977 - 2982
[3] Patent: CN104031034, 2017, B, . Location in patent: Paragraph 0035-0040
  • 138
  • [ 67-56-1 ]
  • [ 141-97-9 ]
  • [ 459-57-4 ]
  • [ 216690-15-2 ]
Reference: [1] Tetrahedron Letters, 2000, vol. 41, # 30, p. 5647 - 5651
  • 139
  • [ 141-97-9 ]
  • [ 188781-08-0 ]
Reference: [1] European Journal of Medicinal Chemistry, 2013, vol. 66, p. 314 - 323
[2] Patent: WO2016/37578, 2016, A1,
  • 140
  • [ 141-97-9 ]
  • [ 60481-51-8 ]
  • [ 277299-70-4 ]
YieldReaction ConditionsOperation in experiment
76% With sodium bicarbonate; sodium acetate In diethyl ether; acetic acid f
1-(3,4-Dimethylphenyl)-3-methyl-3-pyrazolin-5-one
A solution of 3,4-dimethylphenylhydrazine hydrochloride (17.7 g; 0.1 mol.), ethyl acetoacetate (13.0 g; 0.1 mol.) and sodium acetate (8.2 g; 0.1 mol.) in glacial acetic acid (250 mL) was stirred and heated under reflux for 24 h.
The mixture was cooled and evaporated and the residue dissolved in diethyl ether (IL) and carefully washed with sat. aqu. sodium hydrogen carbonate (5*200 mL).
The ethereal layer was evaporated to afford the title compound (15.4 g; 76percent).
1H NMR (300 MHz, d6-DMSO) δ11.30 (br s, 1H), 7.49 (d, J=1.4 Hz, 1H), 7.43 (dd, J=8.2 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 5.31 (s, 1H), 2.20 (s, 3H), 2.22 (s, 3H), 2.08 (s, 3H); MS(ES) m/z 203 [M+H].
76% With sodium acetate In acetic acid for 24 h; Heating / reflux A solution of 3,4-dimethylphenylhydrazine hydrochloride (17.7 g; 0.1 mol.), ethyl acetoacetate (13.0 g; 0.1 mol.) and sodium acetate (8.2 g; 0.1 mol.) in glacial acetic acid; (250 mL) was stirred and heated under reflux for 24 h. [0378] The mixture was cooled and evaporated and the residue dissolved in diethyl ether (1L) and carefully washed with sat. aqu. sodium hydrogen carbonate (5.x.200 mL). The ethereal layer was evaporated to afford the title compound (15.4 g; 76percent). 1H NMR (300 MHz, d6-DMSO) δ 11.30 (br s, 1H), 7.49 (d, J=1.4 Hz, 1H), 7.43 (dd, J=8.2 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 5.31 (s, 1H), 2.20 (s, 3H), 2.22 (s, 3H), 2.08 (s, 3H); MS(ES) m/z 203 [M+H].
76% for 24 h; Reflux A solution of 3,4-dimethylphenylhydrazine hydrochloride (17.7 g; 0.1 mol.), ethyl acetoacetate (13.0 g; 0.1 mol.) and sodium acetate (8.2 g; 0.1 mol.) in glacial acetic acid; (250 mL) was stirred and heated under reflux for 24h. The mixture was cooled and evaporated and the residue dissolved in diethyl ether (1L) and carefully washed with saturated aqueous sodium hydrogen carbonate (5 x 200 mL). The ethereal layer was evaporated to afford the title compound (15.4 g; 76percent).
Reference: [1] Patent: US2004/53299, 2004, A1,
[2] Patent: US2004/19190, 2004, A1, . Location in patent: Page 17
[3] Patent: WO2016/35018, 2016, A1, . Location in patent: Page/Page column 13
  • 141
  • [ 141-97-9 ]
  • [ 13636-53-8 ]
  • [ 277299-70-4 ]
Reference: [1] Patent: US6552008, 2003, B1,
  • 142
  • [ 607-68-1 ]
  • [ 141-97-9 ]
  • [ 425638-74-0 ]
YieldReaction ConditionsOperation in experiment
54%
Stage #1: With sodium hydride In tetrahydrofuran at 0℃; for 1 h;
Stage #2: for 0.5 h; Reflux
Stage #3: for 0.333333 h;
Λ/, ν-dimethylaniline (33.4 g, 276 mmol, 1 .0 eq) was added dropwise to a solution of 2,4 (1 H, 3H)-quinazolinedione (50 g, 276 mmol, 1 .0 eq) in POCI3 (300 ml) and the mixture was heated to reflux for 3 hrs. The solution was cooled to room temperature, poured onto ice water and the resulting precipitate was filtered off and washed with water. The solid was dissolved in EtOAc and washed with water and brine. The organic fraction was dried over Na2S04, filtered, concentrated under reduced pressure, and washed with petroleum ether to give the corresponding dichloro-derivative (20 g, 34percent yield).Ethyl-3-oxobutanoate (31.2 g, 240 mmol, 2.0 eq) was added dropwise to a suspension of NaH (6 g, 156 mmol, 1 .3 eq) in THF (520 ml) at 0 °C. After stirring at 0 °C for 1 h and removal of THF under reduced pressure, a solution of 2,4-dichloroquinazoline (24 g, 120 mmol, 1.0 eq) in toluene (350 ml) was added and the reaction mixture was heated to reflux for 30 min. After removal of toluene under reduced pressure, NH4OH (320 ml) was added. After stirring for 20 min, the mixture was concentrated to remove NH4OH. EtOAc (100 ml) and water (50 ml) were added to the mixture, that was filtered to give 2-(2- chloroquinazolin-4-yl)acetamide (14.4 g, 54 percent yield).1 -Methylpiperazine (34 g, 339 mmol, 5.0 eq) was added to a solution of 2-(2- chloroquinazolin-4-yl)acetamide (14.4 g, 65 mmol, 1.0 eq) in NMP (250 ml) and stirred at 50 °C for 30 min. After cooling to room temperature, EtOAc (100 ml) was added and the suspension was filtered to give 2-(2-(4-methylpiperazin-1 -yl)quinazolin-4-yl)acetamide (10.5 g, 55 percent yield).fert-BuOK (215 ml_, 121 mmol, 3.0 eq) was added to a solution of 2-(2-(4-methylpiperazin- 1 -yl)quinazolin-4-yl)acetamide (10.5 g, 36.8 mmol, 1.0 eq) and Intermediate 2 (10.5 g, 40.5 mmol, 1.1 eq) in anhydrous THF (250 ml) at room temperature and the mixture was stirred for about 30 min, quenched with water, extracted with EtOAc, washed with brine, dried over Na2S04, concentrated and purified by column chromatography (silicagel) to give the methyl-ester of intermediate 8 (1 1 g, 60 percent yield).
Reference: [1] Journal of Medicinal Chemistry, 2009, vol. 52, # 20, p. 6193 - 6196
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 17, p. 6028 - 6039
[3] Patent: WO2013/4709, 2013, A1, . Location in patent: Page/Page column 54-55
[4] Patent: US2003/69424, 2003, A1,
  • 143
  • [ 141-97-9 ]
  • [ 108381-23-3 ]
Reference: [1] Patent: WO2012/123467, 2012, A1,
[2] Patent: US2013/197059, 2013, A1,
[3] European Journal of Medicinal Chemistry, 2015, vol. 101, p. 266 - 273
[4] Patent: WO2016/37578, 2016, A1,
[5] Patent: US2018/99940, 2018, A1,
  • 144
  • [ 141-97-9 ]
  • [ 4637-24-5 ]
  • [ 203186-58-7 ]
YieldReaction ConditionsOperation in experiment
3.6 g at 60℃; for 3 h; To a solution of ethyl acetoacetate (2.6 g, 20 mmol) in ethanol (10 mL) was added N,N-Dimethylformamide dimethyl acetal (2.5 g, 21 mmol). The mixture was allowed to stir at 60 °C for 3 h, then cooled to room temperature and concentrated to give a crude product (3.6 g, 97percent), which was used without further purification.
Reference: [1] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 5, p. 1038 - 1043
[2] Patent: WO2017/151786, 2017, A1, . Location in patent: Paragraph 00230
  • 145
  • [ 141-97-9 ]
  • [ 126-81-8 ]
  • [ 3218-36-8 ]
  • [ 1099644-42-4 ]
YieldReaction ConditionsOperation in experiment
97% With ammonium acetate In neat (no solvent) at 80℃; for 0.166667 h; Green chemistry General procedure: A mixture of aromatic aldehyde (1 mmol), dimedone (0.14 g, 1 mmol), ethyl acetoacetate (0.13 g, 1 mmol), ammonium acetate (0.115 g, 1.5 mmol), and Fe2O3(at)HAP(at)Melamine (0.15 g) was heated at for 80 °C. Completion of the reactions was monitored by TLC (n-hexan/ethyl acetate 10:3). After satisfactory completion of the reaction and cooling, the reaction mixture was washed with hot ethel acetate and the catalyst was removed by a magnetic field. The solid residue was isolated and purified by recrystallization in hot EtOH.
96% With ammonium acetate In neat (no solvent) at 20℃; for 0.166667 h; Green chemistry General procedure: The nickel(II) Schiff base complex immobilized on MWCNTs as a heterogeneous catalyst (0.005 g) was added to a mixture of aromatic aldehyde (1 mmol), 1,3-dione (1 mmol), ethyl acetoacetate (1 mmol), and ammonium acetate (1.5 mmol) in a round bottom flask and the resulting mixture was stirred magnetically under solvent-free conditions at room temperature. After reaction, as observed by TLC (n-hexane/ethyl acetate: 5/2), ethyl acetate (5 mL) was added to the reaction mixture, stirred and refluxed for 10 min, washed with ethanol (5 mL) and decanted to separate catalyst from other materials (the reaction mixture was soluble in hot ethyl acetate and nanocatalyst was insoluble). The solvent of organic layer was evaporated and the crude product was purified by recrystallization from ethanol. In this study, nanoheterogeneous catalyst was recycled and reused for seven times without significant loss of its catalytic activity.
96% With ammonium acetate; ascorbic acid In neat (no solvent) at 80℃; for 5 h; Green chemistry General procedure: A mixture of aldehyde (1 mmol), cyclic 1,3-diketone (1 mmol), ethyl acetoacetate (1 mmol), ammonium acetate (1 mmol), and ascorbic acid (5percent mol) was stirred at 80 °C under solvent-free conditions for appropriate time (Table 3). After complete conversion as indicated by TLC, the reaction mixture was cooled to room temperature, poured onto ice-cold water (10 mL), and stirred for about 10 min. The formed solid was filtered off, washed with cold water, and purified by simple crystallization in ethanol.
88% With bismuth(III) bromide; ammonium acetate In ethanol at 20℃; for 3 h; General procedure: A homogeneous mixture of p-tolualdehyde (0.5000 g,4.16 mmol), dimedone (0.6417 g, 4.58 mmol, 1.1 equiv), ethyl acetoacetate(0.5968 g, 0.58 mL, 4.58 mmol, 1.1 equiv), and ammonium acetate (0.3528 g,4.58 mmol, 1.1 equiv) was stirred in anhydrous ethanol (10.0 mL) at roomtemperature as BiBr3 (0.0373 g, 2.0 mol percent) was added. The reaction progresswas monitored by TLC (2,4-DNP stain). After 1.5 h, the reaction mixture waspoured onto 20 g of ice and the resulting yellow precipitate was collected viasuction filtration. The crude product was recrystallized using anhydrousethanol (approximately 30 mL) to yield 1.2694 g (86percent yield) of a slightly offwhite,powdery compound. Mpt: 258–259 C (Lit: 258–259 C).
38% With ammonium acetate; iodine In ethanol at 20℃; General procedure: 1 eq. of a cyclic 1,3-dicarbonyl compound 2, 1 eq. of the desired aldehyde 5, 1 eq. of a 1,3-dicarbonyl compound 3, 1 eq. of dried NH4OAc and 0.3 eq. of iodine were stirred in EtOH (2.5 mL/mmol) overnight at room temperature. The solvent was evaporated and the residue was dissolved in EtOAc. The organic layer was washed twice with a saturated solution of NaS2O3 and brine, dried over MgSO4 and concentrated under reduced pressure. The crude material was purified by recrystallization or flash chromatography.

Reference: [1] RSC Advances, 2014, vol. 4, # 101, p. 57662 - 57670
[2] Research on Chemical Intermediates, 2015, vol. 41, # 10, p. 7227 - 7244
[3] Applied Organometallic Chemistry, 2016, vol. 30, # 5, p. 311 - 317
[4] Journal of Coordination Chemistry, 2017, vol. 70, # 2, p. 340 - 360
[5] Synthetic Communications, 2017, vol. 47, # 12, p. 1185 - 1191
[6] RSC Advances, 2016, vol. 6, # 110, p. 108896 - 108907
[7] RSC Advances, 2015, vol. 5, # 68, p. 55303 - 55312
[8] Tetrahedron Letters, 2015, vol. 56, # 27, p. 4060 - 4062
[9] Chemical Communications, 2011, vol. 47, # 1, p. 529 - 531
[10] RSC Advances, 2017, vol. 7, # 89, p. 56764 - 56770
[11] European Journal of Medicinal Chemistry, 2015, vol. 95, p. 249 - 266
Same Skeleton Products
Historical Records

Similar Product of
[ 141-97-9 ]

Chemical Structure| 77504-74-6

A1267981[ 77504-74-6 ]

Ethyl 3-oxobutanoate-2,4-13C2

Reason: Stable Isotope

Chemical Structure| 84508-55-4

A1269517[ 84508-55-4 ]

Ethyl 3-oxobutanoate-1,2,3,4-13C4

Reason: Stable Isotope

Chemical Structure| 89186-80-1

A1267963[ 89186-80-1 ]

Ethyl acetoacetate-3,4-13C2

Reason: Stable Isotope

Chemical Structure| 61973-42-0

A1354505[ 61973-42-0 ]

Ethyl acetoacetate-3-13C

Reason: Stable Isotope

Chemical Structure| 77504-73-5

A1375485[ 77504-73-5 ]

Ethyl 3-oxobutanoate-1,3-13C2

Reason: Stable Isotope

Chemical Structure| 100548-44-5

A1375489[ 100548-44-5 ]

Ethyl 3-oxobutanoate-4-13C

Reason: Stable Isotope

Chemical Structure| 100548-43-4

A1502786[ 100548-43-4 ]

Ethyl 3-oxobutanoate-1-13C

Reason: Stable Isotope

Related Functional Groups of
[ 141-97-9 ]

Aliphatic Chain Hydrocarbons

Chemical Structure| 4949-44-4

[ 4949-44-4 ]

Ethyl 3-oxopentanoate

Similarity: 0.96

Chemical Structure| 67342-99-8

[ 67342-99-8 ]

Ethyl 3-oxododecanoate

Similarity: 0.96

Chemical Structure| 3249-68-1

[ 3249-68-1 ]

Ethyl Butyrylacetate

Similarity: 0.96

Chemical Structure| 105-45-3

[ 105-45-3 ]

Methyl 3-oxobutanoate

Similarity: 0.92

Chemical Structure| 539-88-8

[ 539-88-8 ]

Ethyl 4-oxopentanoate

Similarity: 0.89

Esters

Chemical Structure| 4949-44-4

[ 4949-44-4 ]

Ethyl 3-oxopentanoate

Similarity: 0.96

Chemical Structure| 67342-99-8

[ 67342-99-8 ]

Ethyl 3-oxododecanoate

Similarity: 0.96

Chemical Structure| 3249-68-1

[ 3249-68-1 ]

Ethyl Butyrylacetate

Similarity: 0.96

Chemical Structure| 105-45-3

[ 105-45-3 ]

Methyl 3-oxobutanoate

Similarity: 0.92

Chemical Structure| 539-88-8

[ 539-88-8 ]

Ethyl 4-oxopentanoate

Similarity: 0.89

Ketones

Chemical Structure| 4949-44-4

[ 4949-44-4 ]

Ethyl 3-oxopentanoate

Similarity: 0.96

Chemical Structure| 67342-99-8

[ 67342-99-8 ]

Ethyl 3-oxododecanoate

Similarity: 0.96

Chemical Structure| 3249-68-1

[ 3249-68-1 ]

Ethyl Butyrylacetate

Similarity: 0.96

Chemical Structure| 105-45-3

[ 105-45-3 ]

Methyl 3-oxobutanoate

Similarity: 0.92

Chemical Structure| 539-88-8

[ 539-88-8 ]

Ethyl 4-oxopentanoate

Similarity: 0.89