59288-43-6|5-Hydroxy-6-nitronicotinic 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 [ 59288-43-6 ] Purity: 97% 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 [ 59288-43-6 ]

CAS No. :	59288-43-6
Formula :	C₆H₄N₂O₅
M.W :	184.11
SMILES Code :	O=C(O)C1=CN=C([N+]([O-])=O)C(O)=C1
MDL No. :	MFCD11044358
InChI Key :	OODZZMDHMOPHHY-UHFFFAOYSA-N
Pubchem ID :	18357439

Safety of [ 59288-43-6 ]

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

Computational Chemistry of [ 59288-43-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	2
Num. H-bond acceptors	6.0
Num. H-bond donors	2.0
Molar Refractivity	42.04
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	116.24 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.52
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	0.74
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.39
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.	-1.88
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	-1.81
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-0.41

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.66
Solubility	4.05 mg/ml ; 0.022 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.	-2.76
Solubility	0.32 mg/ml ; 0.00174 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	-0.2
Solubility	115.0 mg/ml ; 0.624 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.	-6.9 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	2.0 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)	2.06

Application In Synthesis of [ 59288-43-6 ]

* 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 [ 59288-43-6 ]

[ 59288-43-6 ] Synthesis Path-Downstream 1~14

2
[ 59288-43-6 ]
[ 20443-98-5 ]
[ 756520-61-3 ]

Yield	Reaction Conditions	Operation in experiment
46%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 4.5h;	2. 2,6-Dichlorobenzyl-6-nitro-5-[(2,6-dichlorobenzyl)oxy]nicotinate (B3): <strong>[59288-43-6]6-nitro-5-hydroxynicotinic acid</strong> (B2) (3.4 g, 18.5 mmol), 2,6-dichlorobenzyl bromide (8.88 g, 37 mmol), DIPEA (5.5 g, 42.5 mmol) were dissolved in DMF (25 mL) in a 250 mL round bottomed flask and the reaction was stirred at room temperature for 4.5 hr and then concentrated under reduced pressure. The resulting mixture was poured into ice and the filtered. The solid collected was dried under reduced pressure to give 4.25 g (46% yield) of B3. MS (APCI) (M+H)+503. 1H-NMR (DMSO-d6) delta 5.47 (s, 2H, ArCH2O), 5.71 (s, 2H, ArCH2O), 7.24-7.43 (m, 6H, Ar-H), 8.26(d, 1H, Ar-H), 8.66(d, 1H, Ar-H).
46%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 4.5h;	2,6-Dichlorobenzyl-6-nitro-5-[(2,6-dichlorobenzyl)oxy]nicotinate (B3): <strong>[59288-43-6]6-nitro-5-hydroxynicotinic acid</strong> (B2) (3.4 g, 18.5 mmol), 2,6-dichlorobenzyl bromide (8.88 g, 37 mmol), DIPEA (5.5 g, 42.5 mmol) were dissolved in DMF (25 mL) in a 250 mL round bottomed flask and the reaction was stirred at room temperature for 4.5 hr and then concentrated under reduced pressure. The resulting mixture was pouredinto ice and the filtered. The solid collected was dried under reduced pressure to give 4.25 g (46% yield) of B3. MS (APCI) (M+H)+ 503. 1HNMR (DMSO-d6) D 5.47 (s, 2H, ArCHaO), 5.71 (s, 2H, ArCHzO), 7.24-7.43 (m, 6H, Ar-H), 8.26(d, 1H, Ar-H), 8.66(d, 1H, Ar-H).

References: [1]Patent: US2006/46991,2006,A1 .Location in patent: Page/Page column 46.
[2]Patent: WO2006/21886,2006,A1 .Location in patent: Page/Page column 77-78.

3
[ 27828-71-3 ]
[ 59288-43-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sulfuric acid; nitric acid; at 0℃; for 48h;Heating;	At 0 C, to a solution of 5- hydroxypyridine-3-carboxylic acid (6.65 g, 47.80 mmol) in sulfuric acid (9 mL) was added HNO3 (12.60 g, 0.2 mol) dropwise. The resulting mixture was stirred for 48 h at 55 C. When the reaction was done, the reaction mixture was diluted with ice water (100 mL). The pH value of the mixture was adjusted to 5 with sodium hydroxide solution (5 M). The resulting mixture was extracted with isopropyl alcohol (200 mL x 3). The organic phases were combined and concentrated under reduced pressure to yield 5-hydroxy-6-nitropyridine-3-carboxylic acid as an yellow solid (8.00 g, 91 %).
64%	With sulfuric acid; nitric acid; at 55 - 60℃; for 96h;	1. 6-Nitro-5-hydroxynicotinic acid (B2): To a solution of 5-hydroxynicotinic acid (B1) (7.0 g, 50 mmol) in concentrated H2SO4 was added 9 mL of fuming HNO3 (90%) (9 mL). The reaction mixture was stirred at 55-60 C. in a sealed tube for four days. The mixture was then poured into ice and the pH was adjusted to 3 with 50% NaOH. MgSO4 was added to saturate the aqueous mixture, which was then extracted with isopropyl alcohol (4*45 mL). After the removal of isopropyl alcohol under reduced pressure, 5.93 g (64% yield) of B2 was obtained as a yellow solid. MS (APCI), (M+H)+185. 1H-NMR (DMSO-d6) delta 8.01 (d, 1H, Ar-H), 8.41(d, 1H, Ar-H).
64%		6-Nitro-5-hydroxynicotinic acid (B2): To a solution of 5-hydroxynicotinic acid (B1) (7.0 g, 50 mmol) in concentrated H2S04 was added 9 mL of fuming HN03 (90%) (9 mL), The reaction mixture was stirred at 55-60C in a sealed tube for four days. The mixture was then poured into ice and the pH was adjusted to 3 with 50% NaOH. MgS04 was added to saturate the aqueous mixture, which was then extracted with isopropyl alcohol (4x45 mL). After the removal of isopropyl alcohol under reduced pressure, 5.93 g (64% yield) of B2 was obtained as a yellow solid. MS (APCI), (M+H)+ 185. 1HNMR (DMSO-dQ)a 8.01 (d, 1H, Ar-H), 8.41 (d, 1H, Ar-H).

	With sulfuric acid; nitric acid; at 0 - 20℃; for 16h;Sealed tube;	In a sealable tube, 5-hydroxypyridine-3-carboxylic acid (1.00 g, 5.95 mol) was dissolved in concentrated H2SO4 (1.34 mL). Then fuming nitric acid (1.35 mL) was added drop wise at 0-5 C and the reaction mixture brought to room temperature slowly and stirred for 16 hrs before being poured onto ice cold water. The pH was adjusted to 3 with 50% NaOH solution and then extracted with isopropyl alcohol: chloroform (1 :19, 4x45 mL). After separation of layers and removal of solvent under reduced pressure, a pale yellow solid was obtained (1.2 g), consisting of a mixture of starting material and 5-hydroxy-6- nitropyridine-3-carboxylic acid in a 2:3 ratio
43 g	With sulfuric acid; nitric acid; at 20 - 30℃; for 14h;	The 89.6 ml nitric acid (65% a) slowly added to 560 ml sulfuric acid (96% a) in, from the internal temperature does not exceed 30 C. Therefore, to divide at room temperature by adding 70g5-hydroxy nicotinic acid (CAS5006-66-6), and the mixture is stirred 14 hours. The mixture is poured into a large amount of ice water, and the obtained precipitate K1 leach. The filtrate is the use of aqueous sodium hydroxide solution to pH= 3, extracted with ethyl acetate 3 times. The combined organic phase is washed with water and dried with sodium sulfate. Remove the solvent in a vacuum. A residue by another K2. Merger of the two parts of the sediment, produce 43g5-hydroxy-6-nitro-pyridine-3-carboxylic acid.

References: [1]Patent: WO2019/79373,2019,A1 .Location in patent: Paragraph 00274.
[2]Patent: US2006/46991,2006,A1 .Location in patent: Page/Page column 45-46.
[3]Patent: WO2006/21886,2006,A1 .Location in patent: Page/Page column 77.
[4]Patent: WO2014/184234,2014,A1 .Location in patent: Page/Page column 55; 56.
[5]Patent: CN105555786,2016,A .Location in patent: Paragraph 0241.

4
[ 59288-43-6 ]
methyl 6-amino-5-methoxypyridine-3-carboxylate [ No CAS ]

References: [1]Patent: WO2014/184234,2014,A1 .
[2]Patent: CN105555786,2016,A .

5
[ 59288-43-6 ]
[ 74-88-4 ]
methyl 5-methoxy-6-nitropyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%		This mixture was dissolved in DMF (7 mL) and K2C03 (1.50 g, 10.9 mmol) was added.The reaction mixture was stuffed at room temperature for 15 mm, cooled to 5-10C andmethyl iodide (0.680 mL, 10.9 mmol) as a solution in DMF (3 mL) was added slowly.The reaction mixture was stuffed at room temperature for 3 more hours, then poured intoice cold water. A yellow solid precipitated, which was filtered and washed sequentiallywith water then hexanes and dried under vacuum to afford methyl 5-methoxy-6- nitropyridine-3-carboxylate (0.5 g, 43%) as a yellow solid.
8%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h;	Method 22 [00275] <strong>[59288-43-6]5-hydroxy-6-nitropyridine-3-carboxylic acid</strong> : At room temperature, to a solution of <strong>[59288-43-6]5-hydroxy-6-nitropyridine-3-carboxylic acid</strong> (4.80 g, 26.07 mmol) in N,N-dimethylformamide (20 mL) was added potassium carbonate (8.5 g, 61.50 mmol), then iodomethane (8.74 g, 61.58 mmol) was added slowly. The resulting mixture was stirred for 16 h at room temperature. When the reaction was done, the reaction mixture was diluted with ice water (60 mL) and extracted with ethyl acetate (100 mL x 3). The organic phases were combined, washed with brine and dried over Na2S04. The solvent was removed under reduced pressure and the residue was purified by flash chromatography eluting with EtOAc in petroleum ether (0 % to 56 % gradient) to yield methyl 5- methoxy-6-nitropyridine-3-carboxylate as an yellow solid (438 mg, 8%). MS: m/z = 213.1 [M+H]+.

References: [1]Patent: WO2014/184234,2014,A1 .Location in patent: Page/Page column 56.
[2]Patent: WO2019/79373,2019,A1 .Location in patent: Paragraph 00274; 00275.

6
[ 59288-43-6 ]
methyl 6-[(1-cyclopentyl-2-ethyl-1,2,3,4-tetrahydro-4-methyl-3-oxopyrido[3,4-b]pyrazin-7-yl)amino]-5-methoxypyridin-3-carboxylate [ No CAS ]