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Chemical Structure| 4093-88-3 Chemical Structure| 4093-88-3

Structure of 4093-88-3

Chemical Structure| 4093-88-3

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Product Details of [ 4093-88-3 ]

CAS No. :4093-88-3
Formula : C6H7N3O2
M.W : 153.14
SMILES Code : O=[N+](C1=CC=CN=C1NC)[O-]
MDL No. :MFCD00223335
InChI Key :SILGRKFIVIVPKA-UHFFFAOYSA-N
Pubchem ID :556349

Safety of [ 4093-88-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 4093-88-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 42.36
TPSA ?

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

70.74 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.17
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

1.55
Log Po/w (WLOGP)?

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

0.84
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.

0.25
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

-1.12
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.54

Water Solubility

Log S (ESOL):?

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

-2.04
Solubility 1.4 mg/ml ; 0.00917 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.65
Solubility 0.347 mg/ml ; 0.00226 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

-1.83
Solubility 2.27 mg/ml ; 0.0148 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.

-6.13 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)

2.16

Application In Synthesis of [ 4093-88-3 ]

* 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 [ 4093-88-3 ]
  • Downstream synthetic route of [ 4093-88-3 ]

[ 4093-88-3 ] Synthesis Path-Upstream   1~9

  • 1
  • [ 5470-18-8 ]
  • [ 74-89-5 ]
  • [ 4093-88-3 ]
YieldReaction ConditionsOperation in experiment
100% at 80℃; for 8 h; Sealed tube To a solution of 3-nitro-2-chloropyridine (4.0 g, 25.2 mmol) in 15 mL 2-methoxyethanol was added methylamine (2.0 M in THF, 32 mL). The reactionwas stirred for 8 hr at 80 °C in a sealed tube. After cooling to rt, the reaction mixture was evaporated to afford 15 quantitatively (3.6 g, 23.2 mmol). 1H NMR (500 MHz, CDCl3) δ 8.47 – 8.37 (m, 2H), 8.20 (s, 1H), 6.64 (dd, J = 8.3, 4.4 Hz, 1H), 3.17 (d, J = 4.8 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 156.0, 153.5, 135.4, 111.7, 28.4. HRMS (ESI+) m/z calcd for C6H8N3O2+ 154.0617, found 154.0610.
98.5% at 0 - 20℃; for 3 h; Methylamine (33percent in EtOH) (1 10 mL, 883 mmol) was placed in a 500 mL three necked round bottom flask. It was cooled to 0 °C using ice bath. 2-chloro-3-nitropyridine (20 g, 126 mmol) was added to the above solution in portions as this is an exothermic reaction. After the addition was complete the reaction mixture was stirred for 2 h at 0 °C and later 1 h at room temperature. Solvent was concentrated and residue was taken in 500 mL of water and extracted with EtOAc 3 x 150 mL. Combine organic layer was dried over Na2SC"4, filtered and concentrated to give a bright orangish yellow solid(19 g , 98.5percent).
95.76% With triethylamine In dichloromethane at 20℃; for 5 h; 24 mL of methylamine, 39.5 mL of triethylamine was added to 240 mL of dichloromethane, and 30 g(0.18 mol) of 2-chloro-3-nitropyridine, and the reaction was completed at room temperature for 5 h. After completion of the reaction, the reaction solution was washed three times with waterInto anhydrous sodium sulfate in addition to water, suction filtration, steaming, yellow crystalline solid product 44.8g (yield 95.76percent).
86% With sodium acetate In water; acetonitrile at 20℃; Heating / reflux 2-chloro-3-nitropyridine 70.0 g, 0.44 mol) was dissolved in recently distilled acetonitrile (400 mL) under stirring. Sodium acetate (55.2 g, 0.67 mol) and 30percent aqueous solution of methylamine (111 mL) were added under vigorous stirring. The obtained suspension was stirred at room temperature for 30 min, refluxed for 1 h, and kept overnight at room temperature. The yellow reaction mixture was concentrated under reduced pressure to remove approximately 300 mL of the solvent. The residue was diluted with 20percent aqueous solution of K2CO3 (1 L) under stirring. The yellow precipitate was filtered off, washed with water (3° * 200 mL), and dried to afford W-Methyl-3-nitropyridin-2-amine in 86percent (58.14 g, 0.38 mol) yield as bright yellow crystals.

References: [1] Tetrahedron Letters, 2015, vol. 56, # 44, p. 6097 - 6099.
[2] Patent: WO2012/121936, 2012, A2, . Location in patent: Page/Page column 93.
[3] Patent: CN106831776, 2017, A, . Location in patent: Paragraph 0097; 0098; 0099.
[4] European Journal of Organic Chemistry, 2009, # 22, p. 3753 - 3764.
[5] Acta Chemica Scandinavica, 1993, vol. 47, # 8, p. 805 - 812.
[6] Patent: WO2008/12622, 2008, A2, . Location in patent: Page/Page column 57.
[7] Open Medicinal Chemistry Journal, 2018, vol. 12, # 1, p. 74 - 83.
[8] Chemistry - A European Journal, 2017, vol. 23, # 57, p. 14173 - 14176.
[9] Patent: US4520196, 1985, A, .
[10] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 5, p. 1696 - 1701.
[11] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 20, p. 5493 - 5496.
  • 2
  • [ 5470-18-8 ]
  • [ 4093-88-3 ]
YieldReaction ConditionsOperation in experiment
98.5% With methylamine In ethanol; water Synthesis of N-methyl-3-nitropyridin-2-amine
Methylamine (33percent in EtOH) (110 mL, 883 mmol) was placed in a 500 mL three necked round bottom flask.
It was cooled to 0° C. using ice bath. 2-chloro-3-nitropyridine (20 g, 126 mmol) was added to the above solution in portions as this is an exothermic reaction.
After the addition was complete the reaction mixture was stirred for 2 h at 0° C. and later 1 h at room temperature.
Solvent was concentrated and residue was taken in 500 mL of water and extracted with EtOAc 3*150 mL.
Combine organic layer was dried over Na2SO4, filtered and concentrated to give a bright orangish yellow solid (19 g, 98.5percent).
References: [1] Patent: US2012/228583, 2012, A1, .
  • 3
  • [ 5470-18-8 ]
  • [ 4093-88-3 ]
  • [ 33742-70-0 ]
References: [1] Patent: US5624935, 1997, A, .
  • 4
  • [ 5470-18-8 ]
  • [ 74-89-5 ]
  • [ 4093-88-3 ]
  • [ 73895-39-3 ]
References: [1] Advanced Synthesis and Catalysis, 1999, vol. 341, # 1, p. 75 - 78.
  • 5
  • [ 1480-87-1 ]
  • [ 74-89-5 ]
  • [ 4093-88-3 ]
References: [1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 21, p. 4790 - 4793.
  • 6
  • [ 123-39-7 ]
  • [ 5470-18-8 ]
  • [ 4093-88-3 ]
References: [1] Journal of the Brazilian Chemical Society, 2010, vol. 21, # 8, p. 1439 - 1445.
  • 7
  • [ 79-16-3 ]
  • [ 5470-18-8 ]
  • [ 4093-88-3 ]
References: [1] Journal of the Brazilian Chemical Society, 2010, vol. 21, # 8, p. 1439 - 1445.
  • 8
  • [ 4214-75-9 ]
  • [ 74-88-4 ]
  • [ 4093-88-3 ]
References: [1] Chemische Berichte, 1928, vol. 61, p. 1230[2] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1928, vol. 60, p. 975.
[3] Chemische Berichte, 1928, vol. 61, p. 1230[4] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1928, vol. 60, p. 975.
  • 9
  • [ 90819-94-6 ]
  • [ 7664-93-9 ]
  • [ 4093-89-4 ]
  • [ 4093-88-3 ]
References: [1] Chemische Berichte, 1928, vol. 61, p. 1230[2] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1928, vol. 60, p. 975.
[3] Chemische Berichte, 1925, vol. 58, p. 1717.
 

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Technical Information

Categories

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