4857-42-5|3-Methylisoxazole-5-carboxylic acid| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 4857-42-5 ] Purity: 95% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 4857-42-5 ]

CAS No. :	4857-42-5
Formula :	C₅H₅NO₃
M.W :	127.10
SMILES Code :	O=C(C1=CC(C)=NO1)O
MDL No. :	MFCD00464222
InChI Key :	HXIYCKAAQPHZBM-UHFFFAOYSA-N
Pubchem ID :	853085

Safety of [ 4857-42-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 4857-42-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	5
Fraction Csp3	0.2
Num. rotatable bonds	1
Num. H-bond acceptors	4.0
Num. H-bond donors	1.0
Molar Refractivity	28.43
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	63.33 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.97
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	0.63
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.68
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	-0.4
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.65
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.51

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.37
Solubility	5.42 mg/ml ; 0.0427 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.53
Solubility	3.71 mg/ml ; 0.0292 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-0.96
Solubility	14.0 mg/ml ; 0.11 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.63 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.56

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.27

Application In Synthesis of [ 4857-42-5 ]

* 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.

Downstream synthetic route of [ 4857-42-5 ]

[ 4857-42-5 ] Synthesis Path-Downstream 1~35

1
[ 70753-36-5 ]
[ 4857-42-5 ]

References: [1]Gazzetta Chimica Italiana,1942,vol. 72,p. 99,106.

2
[ 14716-89-3 ]
[ 70753-36-5 ]
[ 4857-42-5 ]

References: [1]Gazzetta Chimica Italiana,1939,vol. 69,p. 536,541.

3
[ 20577-61-1 ]
[ 3405-77-4 ]
[ 4857-42-5 ]

References: [1]Gazzetta Chimica Italiana,1942,vol. 72,p. 411,422.

4
[ 7063-93-6 ]
[ 4857-42-5 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1966,vol. 2,p. 414 - 420.
Zhurnal Organicheskoi Khimii,1966,vol. 2,p. 417 - 423.

5
[ 19999-32-7 ]
[ 4857-42-5 ]

References: [1]Gazzetta Chimica Italiana,1968,vol. 98,p. 203 - 209.

6
[ 13608-39-4 ]
[ 4857-42-5 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1966,vol. 2,p. 1736 - 1739.
Zhurnal Organicheskoi Khimii,1966,vol. 2,p. 1766 - 1769.

7
[ 94165-54-5 ]
[ 4857-42-5 ]

References: [1]Chemical and pharmaceutical bulletin,1962,vol. 10,p. 607 - 611.

8
[ 63366-79-0 ]
[ 4857-42-5 ]

Yield	Reaction Conditions	Operation in experiment
90%		A round bottom flask with magnetic stirrer was charged with 3-methyl-isoxazole-5- carboxylic acid ethyl ester (900 mg, 5.8 mmol) in tetrahydrofuran (2.0 mL). To the reaction was added a solution of sodium hydroxide (465 mg, 11.6 mmol) in water (2 mL), followed by methanol (4 mL). The reaction was stirred at room temperature for 18 - 20 hours under an argon atmosphere. The reaction was transferred to a separatory funnel and the pH adjusted to 2 via addition of IN hydrochloric acid. The mixture was extracted with ethyl acetate (3 x 35 mL) and the combined extractions were washed with brine (1 x 50 mL), dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to yield S-methyl-isoxazole-S-carboxylic acid as a white solid (660 mg, 90percent). The solid was used without purification in the next reaction.

References: [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 8353 - 8357.
Angew. Chem.,2016,vol. 128,p. 8493 - 8497,5.
[2]Patent: WO2006/91674,2006,A1 .Location in patent: Page/Page column 79.
[3]European Journal of Medicinal Chemistry,1992,vol. 27,p. 581 - 593.

9
[ 300-87-8 ]
[ 4857-42-5 ]

References: [1]Russian Journal of Organic Chemistry,1995,vol. 31,p. 386 - 389.
Zhurnal Organicheskoi Khimii,1995,vol. 31,p. 425 - 428.

10
[ 4857-42-5 ]
[ 49783-72-4 ]

Yield	Reaction Conditions	Operation in experiment
	With oxalyl dichloride;N-formyldiethylamine; In dichloromethane; at 20℃; for 0.833333h;	<strong>[4857-42-5]3-Methyl-5-isoxazolecarboxylic acid</strong> (92 mg) was suspended in dry dichloromethane (2 ml) and treated at 20° C. with oxalyl chloride (0.064 ml) and diethyl formamide (1 drop). Effervescence occurred over ca. 10 mins and after 40 mins stirring at room temperature the solution was added dropwise to a solution of 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (198 mg) (e.g. which can be as prepared in Intermediate 16) in anhydrous acetonitrile (4 ml). The mixture was treated with DIPEA (0.128 ml) and stirred at room temperature under nitrogen for 15 h. Dichloromethane (50 ml) was added to the reaction mixture and the solution was washed with dilute aqueous sodium chloride solution (2.x.50 ml). The organic phase was separated using a hydrophobic frit (70 ml) and loaded directly onto an SPE cartridge (10 g, aminopropyl) which had been pre-washed with methanol. The cartridge was eluted with methanol (.x.2) and the fractions collected and blown down/evaporated to dryness. The residual gum was dissolved in dichloromethane and purified by SPE cartridge (10 g, silica) on a Flashmaster 2 eluting with a gradient of 0-100percent ethyl acetate in cyclohexane over 40 mins. Two fractions (from two chromatographic peaks) were collected and evaporated separately, and each was purified by mass directed autoprep HPLC. Relevant fractions from each were evaporated to dryness. The two residual gums (125 mg and 48 mg respectively) were combined and purified by SPE cartridge (2 g, aminopropyl) which had been pre-washed with methanol. Elution with methanol (.x.2), collection of methanol, and evaporation to dryness gave the title compound N-[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-3-methyl-5-isoxazolecarboxamide as a white foam (173 mg). LCMS showed MH+=413; TRET=2.20 min.

References: [1]Russian Journal of Organic Chemistry,1995,vol. 31,p. 386 - 389.
Zhurnal Organicheskoi Khimii,1995,vol. 31,p. 425 - 428.
[2]Journal of Medicinal Chemistry,1996,vol. 39,p. 2844 - 2851.
[3]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 2679 - 2684.
[4]Synthetic Communications,2002,vol. 32,p. 425 - 433.
[5]Patent: US2009/131431,2009,A1 .Location in patent: Page/Page column 128-129.
[6]Journal of Medicinal Chemistry,2013,vol. 56,p. 6352 - 6370.

11
[ 135351-18-7 ]
[ 4857-42-5 ]

References: [1]Tetrahedron Letters,2000,vol. 41,p. 293 - 297.
[2]Tetrahedron Letters,2000,vol. 41,p. 293 - 297.

12
[ 135351-33-6 ]
[ 4857-42-5 ]

References: [1]Tetrahedron Letters,2000,vol. 41,p. 293 - 297.

14
[ 7647-01-0 ]
[ 3405-77-4 ]
[ 4857-42-5 ]

References: [1]Chemische Berichte,1934,vol. 67,p. 638,640.
[2]Diss. <Kiel 1899> S. 17, 29,.

15
[ 4857-42-5 ]
[ 7732-18-5 ]
Raney nickel [ No CAS ]
[ 73227-94-8 ]

References: [1]Gazzetta Chimica Italiana,1950,vol. 80,p. 441,446.

16
[ 4857-42-5 ]
[ 64-17-5 ]
[ 7803-57-8 ]
copper-powder [ No CAS ]
[ 402-61-9 ]

References: [1]Gazzetta Chimica Italiana,1940,vol. 70,p. 240,244.

17
[ 7803-49-8 ]
[ 615-79-2 ]
[ 3405-77-4 ]
[ 4857-42-5 ]

References: [1]Chemische Berichte,1891,vol. 24,p. 3908.
Chemische Berichte,1909,vol. 42,p. 60.

18
[ 135351-22-3 ]
[ 4857-42-5 ]

References: [1]Canadian Journal of Chemistry,2005,vol. 83,p. 1171 - 1177.

19
[ 4857-42-5 ]
[ 64-17-5 ]
[ 63366-79-0 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; at 50℃;	To a solution of 1 (5g) in EtOH(100mL) was added thionyl chloride(3.44mL), and the resulting solution was stirred at 50 °C. After termination of this reaction, the solution was cooled to room temp. and the volatile was removed under reduced pressure. The residue was dissolved in EtOAc and partitioned between Na2CO3 soln. and EtOAc, then extracted with EtOAc. The extraction was washed with water, brine and dried with MgSO4 and concentrated in vacuo to give ethylester(6.3g). To a solution of tetramethylammonium nitrate(6.81g) in CH2Cl2 (40mL)was added trifluoromethanesulfonic acid anhydride(8.41mL). Ethylester(5.17g) in CH2Cl2 (15ml)was added to the solution and the resulting mixture was refluxed overnight. The reaction mixture was cooled to room temp. and added sat. NaHCO3 soln., then partitioned between water and EtOAc and extracted with EtOAc. The extraction was washed with water and brine, dried with MgSO4 and concentrated in vacuo. The residue was purified by silicagel columnchromatography to give 16 (5.38g).

References: [1]Patent: EP1894919,2008,A1 .Location in patent: Page/Page column 23.

20
1,1,1-trichloropentane-2,4-dione [ No CAS ]
[ 4857-42-5 ]

References: [1]Canadian Journal of Chemistry,2005,vol. 83,p. 1171 - 1177.

21
[ 4857-42-5 ]
[ 27144-53-2 ]