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Chemical Structure| 212268-12-7 Chemical Structure| 212268-12-7
Chemical Structure| 212268-12-7

2-Amino-5-fluoro-3-nitropyridine

CAS No.: 212268-12-7

4.5 *For Research Use Only !

Cat. No.: A225088 Purity: 98%

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Product Details of [ 212268-12-7 ]

CAS No. :212268-12-7
Formula : C5H4FN3O2
M.W : 157.10
SMILES Code : NC1=NC=C(C=C1[N+](=O)[O-])F
MDL No. :MFCD04972413
InChI Key :LDYYBZNEWDTDEE-UHFFFAOYSA-N
Pubchem ID :21717339

Safety of [ 212268-12-7 ]

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

Calculated chemistry of [ 212268-12-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 37.42
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

84.73 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.67
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.99
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.14
Log Po/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.

-0.48
Log Po/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

-0.99
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.27

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.78
Solubility 2.64 mg/ml ; 0.0168 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.

-2.36
Solubility 0.689 mg/ml ; 0.00439 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

-1.31
Solubility 7.64 mg/ml ; 0.0486 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.

-6.56 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.

0.55

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)

2.13

Application In Synthesis of [ 212268-12-7 ]

* 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 [ 212268-12-7 ]

[ 212268-12-7 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 212268-12-7 ]
  • [ 136888-21-6 ]
YieldReaction ConditionsOperation in experiment
(Reference Example 2-2) 5-Fluoro-3-nitropyridine-2-amine (2.66 g) suspended in concentrated hydrochloric acid (35 ml) was cooled to -15C, and an aqueous solution (7 ml) of sodium nitrite (2.57 g) was added dropwise over 10 minutes. After stirring at -10C for 1 hour, and further stirring at room temperature for 1 hour, under ice cooling a 30% aqueous sodium hydroxide solution was added for neutralization. The insolubles were collected by filtration, washed with water, air-dried, and then redissolved in ethyl acetate, before the insolubles were filtered off. The filtrate was concentrated under reduced pressure to afford 2-chloro-5-fluoro-3-nitropyridine (1.41 g). 1H NMR (400 MHz, CDCl3) delta: 8.03 (dd, 1H, J = 6.6, 2.7 Hz), 8.55 (d, 1H, J = 2.7 Hz).
  • 2
  • [ 136888-21-6 ]
  • [ 212268-12-7 ]
YieldReaction ConditionsOperation in experiment
47 g With sodium azide; copper(ll) sulfate pentahydrate; sodium carbonate; sodium L-ascorbate; L-proline; In water; dimethyl sulfoxide; at 70℃; for 24h; In a high-pressure reactor, 85 g (0.5 mol) of 2,3-dichloro-5-fluoropyridine was added to 200 mL of ammonia water.Set the temperature to 180 C, high pressure reaction 24h,TLC detects the reaction of the raw material completely.The solvent was evaporated to give 2-chloro-5-fluoro-3-aminopyridine 65 g;2-chloro-5-fluoro-3-aminopyridine 65 g (0.45 mol)Placed in 900 mL round bottom flask in acetonitrile,Aqueous buffer solution 450mL (0.6M K2CO3-4x10-4M EDTA disodium salt) was added successively,Acetonitrile 350mL (3mol) and 30% H2O2 in water290mL (3mol),The reaction mixture was stirred at room temperature for 1 hour and extracted with ethyl acetate (3 x 300 mL).Combine organic layers,Dry with anhydrous Na2SO4,Remove the solvent under vacuum to obtain the product of sufficient purity <strong>[136888-21-6]2-chloro-5-fluoro-3-nitropyridine</strong>65g;To a solution of <strong>[136888-21-6]2-chloro-5-fluoro-3-nitropyridine</strong> 65 g (0.35 mol) in DMSO/H2O (9:1, 3500 mL) was added L-Proline 230g (2mol),Na2CO3 210g (2mol),NaN3 230g (3.5mol),Sodium ascorbate 350g (1.75mol) andCuSO4·5H2O500g (2 mol);The mixture was stirred in an oil bath at 70 C for 24 hours.Then pour the mixture into 10,000 mL of ice water.The solid product was filtered and crystallized to obtain 47 g of 2-amino-5-fluoro-3-nitropyridine.
With sodium azide; copper(ll) sulfate pentahydrate; sodium carbonate; sodium L-ascorbate; L-proline; In water; dimethyl sulfoxide; at 70℃; for 24h; In a high-pressure reaction vessel, 2,3-dichloro-5-fluoropyridine 85g (0.5 mol) was added to 200 mL of ammonia water, and the temperature was set at 180 C., and the reaction under high pressure was performed for 24 h. The reaction of the starting material was complete by TLC, and the solvent was swirled to obtain 2- Chloro-5-fluoro-3-aminopyridine 65g;Place 2-chloro-5-fluoro-3-aminopyridine 65 g (0.45 mol) in a 900 mL round-bottomed flask in acetonitrile, and add 450 mL of water buffer solution (0.6 M K2CO3-4×10-4 M EDTA disodium salt). 350 mL (3 mol) of acetonitrile and 290 mL (3 mol) of a 30% H2O2 aqueous solution, and the reaction mixture was stirred at room temperature for 1 hour and extracted with ethyl acetate (3 x 300 mL). The organic layers were combined and dried over anhydrous Na2SO4. The solvent was removed to give a sufficiently pure product, <strong>[136888-21-6]2-chloro-5-fluoro-3-nitropyridine</strong>, 65 g;To a solution of 65 g (0.35 mol) of <strong>[136888-21-6]2-chloro-5-fluoro-3-nitropyridine</strong> in DMSO/H2O (mass ratio 9:1, 3500 mL) was added L-proline 230 g (2 mol), Na2CO3 210 g (2 mol), NaN3 230 g (3.5 mol), sodium ascorbate 350 g (1.75 mol) and CuSO4.5H2O 500 g (2 mol); the mixture was stirred in an oil bath at 70C for 24 hours, and then the mixture was poured into 5000 mL of ice water to give a solid product. Filter and crystallize to obtain 47g of 2-amino-5-fluoro-3-nitropyridine; add 2-amino-5-fluoro-3-nitropyridine to the aqueous solution of sulfuric acid, add a certain amount of chloroacetic acid, and heat to 120C. After TLC monitored the reaction of the raw materials, the reaction mixture was extracted with methylene chloride. The pH of the organic phase was adjusted to 7-8 with a saturated sodium carbonate solution, and the organic phase was concentrated to obtain 2-amino-5-fluoro-pyridine.
 

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