Home Cart 0 Sign in  
X

[ CAS No. 13246-52-1 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 13246-52-1
Chemical Structure| 13246-52-1
Chemical Structure| 13246-52-1
Structure of 13246-52-1 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 13246-52-1 ]

Related Doc. of [ 13246-52-1 ]

Alternatived Products of [ 13246-52-1 ]

Product Details of [ 13246-52-1 ]

CAS No. :13246-52-1 MDL No. :MFCD03265450
Formula : C8H12O4 Boiling Point : -
Linear Structure Formula :- InChI Key :JGFBKJBAYISHAG-UHFFFAOYSA-N
M.W : 172.18 Pubchem ID :61590
Synonyms :

Calculated chemistry of [ 13246-52-1 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.62
Num. rotatable bonds : 6
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 42.25
TPSA : 60.44 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.86 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.78
Log Po/w (XLOGP3) : 0.69
Log Po/w (WLOGP) : 0.49
Log Po/w (MLOGP) : 0.02
Log Po/w (SILICOS-IT) : 1.18
Consensus Log Po/w : 0.83

Druglikeness

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

Water Solubility

Log S (ESOL) : -0.95
Solubility : 19.5 mg/ml ; 0.113 mol/l
Class : Very soluble
Log S (Ali) : -1.54
Solubility : 5.01 mg/ml ; 0.0291 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.45
Solubility : 6.1 mg/ml ; 0.0354 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.86

Safety of [ 13246-52-1 ]

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

Application In Synthesis of [ 13246-52-1 ]

* 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 [ 13246-52-1 ]
  • Downstream synthetic route of [ 13246-52-1 ]

[ 13246-52-1 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 95-92-1 ]
  • [ 78-93-3 ]
  • [ 13246-52-1 ]
YieldReaction ConditionsOperation in experiment
67.4% With sodium In ethanol at 0 - 20℃; General procedure: A mixture of ketone 15(0.087 mol), diethyl oxalate 16(0.087mol),thinly sliced sodium (0.047mol) in ethanol (55 mL) was first stirred at 0° and then stirred over night at room temperature. After complication, the mixture was acidified(pH3.0,with 20percent H2SO4), filtered and extracted with dichloromethane.The organic phase was dried and concentrated under vacuum to obtainan yellow or orange liquid 17a-e. The 1,3-diketone 17a-e(0.025mol) was dissolved in methanol (10mL),then added dropwise to a cooled solution(0°C) of hydrazinobenzene(0.025 mol) in methanol (30mL). The reaction was stirred for an hour at room temperature, refluxed for 2h,and the solvent was evaporated under reduced pressure. The residual liguid was purified by column chromatography (a5percent gradient of ethyl acetate in hexanes over a column of silica gel) to afford immediate 18a-e.To obtain the acid 19a-e, a solution of 18a-e(0.007 mol) was saponified through adding7ml 6 mol/L NaOH and stirring at 80°Cfor 2 h.The mixture was acidified (pH1–2) with concentrated hydrochloric acid and filtered to afford 19a-e.To a solution of 19a-e(0.010mol) in 15ml DMF, NCS (0.010mol) was added.The reaction mixture was heated at 90°C for 1hand then added to ice water(50ml), and filtered t oobtain 4-chlorosubstituted carboxylic acids 20a-e. The amide derivatives 21-38 were prepared through the acyl chlorides derived from 19 a-e or 20a-e. A solution of 19a-e or 20a-e(0.004mol) in thionyl chloride(10mL) was refluxed for 5 h and then concentrated under vacuum. The crude acylchloride was added dropwise to a cooled solution(0°C) of substituted aniline (0.004mol) and TEA (0.008mol)in dichloromethane (10mL). The mixture was stirred overnight at room temperature, and then purified on a column of silica using a gradient of ethylacetate in hexanes to afford the pure products.The yields of imtermediate 17a-e, 18a-e, 19a-e and 20a-e are listed intable 1S.
66% With sodium ethanolate In ethanol at 0 - 80℃; Sodium ethoxide (10 g, 147 mmol) is combined with absolute EtOH (65 mL) in a dry flask, under nitrogen and heated to 70° C. to aid dissolution. The mixture is cooled to 0° C., treated drop-wise with a mixture of 2-butanone (13.16 mL, 147 mmol) and diethyl oxylate (19.96 mL, 147 mmol) and warmed to RT. The mixture is stirred for 1 h, then heated to 80° C. for 45 min. The mixture is cooled to RT and concentrated to dryness. The resulting mixture is partitioned between water (200 ML) and EtOAc (3.x.70 mL). The aqueous layer is acidified to pH 2 with dilute H2SO4, extracted with Et2O (3.x.50 mL), dried (Na2SO4) and concentrated to afford 16.7 g (66percent yield) of ethyl 2,4-dioxohexanoate as an amber oil. MS (Cl) m/z: 173 (M+H)+. Ethyl 2,4-dioxohexanoate (11.22 g, 65.15 mmol) is combined with hydroxylamine hydrochloride (13.58 g, 195.5 mmol) in EtOH (200 mL), heated to reflux for 1.5 h, cooled, and concentrated to dryness. The residue is partitioned between H2O (150 mL) and EtOAc (2.x.150 mL) and the combined organics are dried (MgSO4) and concentrated to an amber oil (10.57 g). The crude material is chromatographed over 400 g silica gel, eluting with 20percent EtOAc/hexane. The appropriate fractions are combined and concentrated to afford 8.95 g (81percent yield) of ethyl 5-ethylisoxazole-3-carboxylate as a pale oil. HRMS (ESI) calcd for C8H11NO3 +H: 170.0817, found 170.0824 (M+H)+. Sodium hydroxide (10.9 g, 273 mmol) in water (35 mL) is added to a solution of ethyl 5-ethylisoxazole-3-carboxylate (11.6 g, 68 mmol) in MeOH (70 mL). The mixture is stirred at RT for 3 h, concentrated to remove the MeOH, and acidified to pH 2 with concentrated HCl. The acid is extracted with CH2Cl2 (2.x.150 mL) then 10percent MeOH/CH2Cl2 (4.x.150 mL), dried (MgSO4) and concentrated to afford 5.65 g (58percent yield) of 5-ethylisoxazole-3-carboxylic acid as a white solid. MS (Cl) m/z: 142 (M+H)+. 5-Ethylisoxazole-3-carboxylic acid (1.41 g, 10 mmol) is dissolved in benzene (30 mL), treated with oxalyl chloride (3.46 mL, 40 mmol) and heated to reflux for 2 h. The mixture is cooled, concentrated to dryness and the residual benzene is azeotroped off with CH2Cl2. The resulting acid chloride is dissolved in Me2CO (15 mL) and treated with a solution of NaN3 (1.95 g, 30 mmol) in water (7 mL). The mixture is vigorously stirred for 1 h, concentrated to remove the Me2CO, triturated with water, filtered, rinsed with H2O and dried under vacuum to afford 1.46 g (88percent yield) of 5-ethylisoxazole-3-carbonyl azide as a white solid. 1H NMR (CDCl3, 400 MHz): δ 1.34, 2.85, 6.46 ppm. 5-Ethylisoxazole-3-carbonyl azide (294 mg, 1.8 mmol) is combined with 5-chloro-2,4-dimethoxyaniline (332 mg, 1.8 mmol) in anhydrous MeCN (20 mL) and heated to 70° C. for 20 h. The mixture is cooled and the resulting solid is filtered, rinsed with Et2O and dried in a vacuum oven to afford 448 mg (78percent yield) of Example 627 as a white solid. HRMS (ESI) calcd for C14H16N3O4Cl +H: 326.0907, found 326.0909 (M+H)+.
39% With sodium ethanolate In ethanol at 0 - 25℃; for 16 h; [0518] a mixture of compound 33a (46.73 ml, 342.14 mmol) and butan-2-one (30.46 ml, 342.14 mmol) was added dropwise to the solution of naoet (prepared by na (9.5 g) in EtOH (200 ml)) at 0 °C. Then the reaction was stirred at 20-25 °C for 16 hrs. The reaction was adjusted to ph ~ 6-7 with HCl (2m) and then removed the solvent to give a residue, which was diluted with ethyl acetate (500 ml), washed with brine (150 ml), dried over Na2SO4 and concentrated to give the crude product which was purified by flash column chromatography (petroleum ether : ethyl acetate = 1:0 to 10: 1) to give compound 33b (23.0 g, yield: 39.0 percent) as a yellow oil. 1H NMR (CDCl3, 400 mhz) δ 14.34 (br s, 1h), 6.31 (s, 1h), 4.28 (q, 7 = 7.2 hz, 2h), 2.47 (q, 7 = 7.3 hz, 2h), 1.34 - 1.27 (m, 3h), 1.11 (t, 7 = 7.5 hz, 3h).
17 g
Stage #1: With sodium In ethanol at 20℃; for 0.166667 h; Cooling with ice
Stage #2: at 70℃; for 2.5 h;
Sodium (3.18 g) was added portionwise at room temperature in ethanol (60 mL), and stirred until dissolved. Was added dropwise 2-butanonesolution in ethanol (10.0 g) and (30 mL) the reaction mixture under ice cooling, the reaction mixture after stirring for 10 minutes, ethanol was added asolution of diethyl oxalate (20.2g) (30mL) . After the reaction mixture for 2.5 hours heated and stirred at 70 , allowed to cool, ethanol was distilled offunder reduced pressure. The residue was diluted with water, acidified with 1.0mol / L hydrochloric acid, and extracted twice with chloroform. Thecombined organic layers were dried over anhydrous sodium sulfate, filtered to give 2,4-di-oxo-hexanoic acid ethyl ester by concentrating (17.0g).

Reference: [1] Synthetic Communications, 2013, vol. 43, # 1, p. 110 - 117
[2] Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 6, p. 1470 - 1479
[3] Chinese Chemical Letters, 2016, vol. 27, # 4, p. 566 - 570
[4] Patent: US2003/236287, 2003, A1, . Location in patent: Page 47, 48
[5] Monatshefte fur Chemie, 2003, vol. 134, # 9, p. 1221 - 1227
[6] Patent: WO2018/64119, 2018, A1, . Location in patent: Paragraph 0518
[7] Journal of Medicinal Chemistry, 1972, vol. 15, p. 429 - 431
[8] Helvetica Chimica Acta, 1947, vol. 30, p. 1349,1366
[9] Chemische Berichte, 1906, vol. 39, p. 1337
[10] Tetrahedron Letters, 1988, vol. 29, # 32, p. 3997 - 4000
[11] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 17, p. 4914 - 4919
[12] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 20, p. 5620 - 5623
[13] Patent: US6020357, 2000, A,
[14] Patent: EP946508, 2009, B1, . Location in patent: Page/Page column 95
[15] Patent: EP1544202, 2005, A1, . Location in patent: Page/Page column 51
[16] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 13, p. 4341 - 4347
[17] Patent: WO2014/139150, 2014, A1, . Location in patent: Page/Page column 80; 81
[18] Patent: WO2014/150114, 2014, A1, . Location in patent: Page/Page column 80; 81
[19] Journal of Antibiotics, 2015, vol. 68, # 6, p. 361 - 367
[20] Patent: TW2016/2115, 2016, A, . Location in patent: Paragraph 4829 - 4831
[21] Patent: CN106608873, 2017, A, . Location in patent: Paragraph 0111-0113
[22] Patent: CN106608872, 2017, A, . Location in patent: Paragraph 0104; 0105
[23] Chemical Papers, 2017, vol. 71, # 11, p. 2053 - 2061
[24] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 1066 - 1076
[25] Journal of Medicinal Chemistry, 2018,
  • 2
  • [ 64-17-5 ]
  • [ 95-92-1 ]
  • [ 78-93-3 ]
  • [ 13246-52-1 ]
YieldReaction ConditionsOperation in experiment
40%
Stage #1: at 0℃; for 0.166667 h;
Stage #2: at 0 - 20℃;
Step 1 : Preparation of Ethyl 2,4-dioxohexanoateTo a suspension of sodium hydride (44 g, 1.10 mol, 60percent in mineral oil) dry ethanol (318 mL, 5.44 mol) was added dropwise at a temperature of 0cC. Ten minutes after the addition was completed and still at 00C, a mixture of 2-butanone (90 mL, 1.0 mol) and diethyl oxalate (136 mL, 1.0 mol) was added dropwise. The reaction mixture was stirred at rt over night. Then, sulfuric acid was added (4N aq., 550 mL, 1.1 mol). The crude product was extracted into diethyl ether. After washing with water and brine, the organic extract was dried over anhydrous magnesium sulfate, followed by filtration and evaporation of the solvent. The residue was subjected to distillation in vacuo. At a boiling point of 68-78°C(2.2-2.6 mbar) the product was obtained as a colorless liquid (68.4 g, 40percent): 1H NMR (400MHz, CDCI3) δ 14.40 (broad, 1H), 6.38 (s, 1H), 4.36 (quart, 2H), 2.53 (quart, 2H), 1.38 (t,3H), 1.17 (t, 3H); DCI(NH3)-MS m/z 173 (MH)+, 190 (M+NH4)+; HPLC RT (Method I) 4.02 min.
Reference: [1] Patent: WO2008/141731, 2008, A2, . Location in patent: Page/Page column 66
  • 3
  • [ 95-92-1 ]
  • [ 78-93-3 ]
  • [ 781-38-4 ]
  • [ 13246-52-1 ]
Reference: [1] Chemische Berichte, 1906, vol. 39, p. 1337
  • 4
  • [ 13246-52-1 ]
  • [ 26308-42-9 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 6, p. 1470 - 1479
[2] Patent: CN106608873, 2017, A,
[3] Patent: CN106608872, 2017, A,
[4] Chemical Papers, 2017, vol. 71, # 11, p. 2053 - 2061
[5] European Journal of Medicinal Chemistry, 2018, vol. 149, p. 170 - 181
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 13246-52-1 ]

Aliphatic Chain Hydrocarbons

Chemical Structure| 5965-53-7

[ 5965-53-7 ]

Diethyl 2-oxopentanedioate

Similarity: 0.97

Chemical Structure| 15933-07-0

[ 15933-07-0 ]

Ethyl 2-oxobutanoate

Similarity: 0.94

Chemical Structure| 13192-04-6

[ 13192-04-6 ]

Dimethyl 2-oxoglutarate

Similarity: 0.91

Chemical Structure| 13395-36-3

[ 13395-36-3 ]

Ethyl 5,5-dimethyl-2,4-dioxohexanoate

Similarity: 0.89

Chemical Structure| 26103-78-6

[ 26103-78-6 ]

Diethyl 2-oxo-3-propylsuccinate

Similarity: 0.86

Esters

Chemical Structure| 5965-53-7

[ 5965-53-7 ]

Diethyl 2-oxopentanedioate

Similarity: 0.97

Chemical Structure| 15933-07-0

[ 15933-07-0 ]

Ethyl 2-oxobutanoate

Similarity: 0.94

Chemical Structure| 13192-04-6

[ 13192-04-6 ]

Dimethyl 2-oxoglutarate

Similarity: 0.91

Chemical Structure| 21080-80-8

[ 21080-80-8 ]

Ethyl 4-cyclopropyl-2,4-dioxobutanoate

Similarity: 0.89

Chemical Structure| 13395-36-3

[ 13395-36-3 ]

Ethyl 5,5-dimethyl-2,4-dioxohexanoate

Similarity: 0.89

Ketones

Chemical Structure| 5965-53-7

[ 5965-53-7 ]

Diethyl 2-oxopentanedioate

Similarity: 0.97

Chemical Structure| 15933-07-0

[ 15933-07-0 ]

Ethyl 2-oxobutanoate

Similarity: 0.94

Chemical Structure| 13192-04-6

[ 13192-04-6 ]

Dimethyl 2-oxoglutarate

Similarity: 0.91

Chemical Structure| 21080-80-8

[ 21080-80-8 ]

Ethyl 4-cyclopropyl-2,4-dioxobutanoate

Similarity: 0.89

Chemical Structure| 13395-36-3

[ 13395-36-3 ]

Ethyl 5,5-dimethyl-2,4-dioxohexanoate

Similarity: 0.89