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Chemical Structure| 6635-90-1 Chemical Structure| 6635-90-1

Structure of 6635-90-1

Chemical Structure| 6635-90-1

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Product Details of [ 6635-90-1 ]

CAS No. :6635-90-1
Formula : C7H8N2O3
M.W : 168.15
SMILES Code : C1=C(OC)N=CC(=C1C)[N+]([O-])=O
MDL No. :MFCD03095075
InChI Key :DJNQRLCFAHKFLZ-UHFFFAOYSA-N
Pubchem ID :243169

Safety of [ 6635-90-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 6635-90-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.29
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 44.52
TPSA ?

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

67.94 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.56
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

1.35
Log Po/w (WLOGP)?

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

1.31
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.

-0.21
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

-0.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.73

Water Solubility

Log S (ESOL):?

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

-1.97
Solubility 1.8 mg/ml ; 0.0107 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.

-2.38
Solubility 0.703 mg/ml ; 0.00418 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

-1.91
Solubility 2.05 mg/ml ; 0.0122 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

Yes
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

Yes
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.

-6.37 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)

1.98

Application In Synthesis of [ 6635-90-1 ]

* 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.

  • Downstream synthetic route of [ 6635-90-1 ]

[ 6635-90-1 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 6635-90-1 ]
  • [ 6635-91-2 ]
YieldReaction ConditionsOperation in experiment
With hydrogen;palladium on activated charcoal; In tetrahydrofuran; at 20℃; for 6h; Reference Example 50 6-Methoxy-4-methylpyridin-3-amine A mixture of 2-methoxy-4-methyl-5-nitropyridine4-Methyl-5-nitro-2-pyrrolidin-1-ylpyridine (1.68 g, 10.0 mmol) and 10% palladium on carbon (168 mg) in tetrahydrofuran (10 mL) was stirred under hydrogen atmosphere at room temperature for 6 hr. Catalyst was removed by filtration and the filtrate was concentrated in vacuo to give the title compound (1.31 g, 9.49 mmol, 95%) as a pale brown solid. 1H NMR (CDCl3) delta 2.16 (s, 3H), 3.28 (brs, 2H), 3.85 (s, 3H), 6.50 (s, 1H), 7.59 (s, 1H).
  • 2
  • tin(II)chloride dihydrate [ No CAS ]
  • [ 6635-90-1 ]
  • [ 6635-91-2 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In acetic acid; b 5-Amino-2-methoxy-4-methylpyridine A mixture of stannous chloride dihydrate (41 g) and concentrated hydrochloric acid (40 ml) was added slowly to a solution of 2-methoxy-4-methyl-5-nitropyridine (5.1 g) in acetic acid (40 ml), maintaining the temperature below 35 C. The resulting mixture was stirred at room temperature for 2 hours, and then allowed to stand overnight in the refrigerator. The solid was collected and both solid and supernatant were separately basified with a 20% sodium hydroxide solution. The product was extracted with chloroform, combined, dried (anhydrous magnesium sulfate) and concentrated to give 3.9 g of the title compound as a solid, suitable for use in the next reaction.
  • 3
  • [ 6635-90-1 ]
  • [ 17288-53-8 ]
YieldReaction ConditionsOperation in experiment
With N,N-dimethyl-formamide dimethyl acetal;palladium; In ethanol; ethyl acetate; A solution of 2-methoxy-4-methyl-5-nitropyridine (4.30 g, 25.57 mmol) and dimethylformamide dimethylacetal (35 ml) was heated at reflux under nitrogen for 40 hours. Ethyl acetate was added to this solution (150 ml), and this mixture was washed with water (150 ml). The aqueous extract was back-extracted with ethyl acetate (100 ml), and the organic extracts were combined, dried (Na2 O4), and evaporated under reduced pressure to yield a purple solid. The solid was dissolved in absolute ethanol (200 ml), and 5% palladium on carbon (3.0 g) was added to this solution which was shaken under a hydrogen atmosphere (3 atm) for 3 hours. The resultant reaction mixture was filtered, and the filtrate was evaporated under reduced pressure. Flash chromatography of the residue yielded compound 9 (2.05 g, 13.84 mmol, 54% last step, 50% overall) as a white crystalline solid: mp, 123-124 C.; IR (KBr) 1625, 1580, 1490, 1460, 1320, 1150 cm-1; 1 H NMR (DMSO-d6) delta 11.28 (br s, 1H), 8.37 (s, 1H), 7.57 (t, J=2.8 Hz, 1H), 6.86 (s, 1H), 6.33 (br m, 1H), 3.82 (s, 3H); 13 C NMR (DMSO-d6) delta 157.2, 136.4, 131.5, 130.7, 130.0, 99.6, 96.8, 53.4; LRMS (m/z, relative intensity) 149 (20), 148 (M+, 98), 147 (100), 119 (46), 118 (79), 117 (26), 105 (31), 91 (15), 70 (16); HRMS calculated for C8 H8 N2 O:148.0657, found: 148.0613.
  • 4
  • [ 6635-90-1 ]
  • [ 4637-24-5 ]
  • [ 17288-53-8 ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; at 130℃; 1. The mixture of 2-methoxy-4-methyl-5-nitropyridine (1.68g, 10.0 mmol) and 1,1- dimethoxy-N,N-dimethylmethanamine (14 Ml, 103 mmol) in 10 mL of DMF was heated at 130C overnight, cooled to RT, diluted with EtOAc, washed with water and brine, dried (MgS04), and concentrated. The residue was dissolved in 70 mL of EtOH. To this solution was added 1.06 g of 10% Pd/C. The mixture was stirred under 1 atm of hydrogen atmosphere over 4 days, filtered through a pad of Celite, and washed with EtOH. The filtrate was concentrated to give crude 5-methoxy-lH-pyrrolo[2,3-c]pyridine (quant). H NMR (399 MHz, DMSO-d6) delta ppm 11.26 (1 H, br. s.), 8.33 (1 H, s), 7.53 (1 H, d, 7=2.7 Hz), 6.73 - 6.88 (1 H, m), 6.32 (1 H, d, 7=3.1 Hz), 3.30 (3 H, s).
 

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Technical Information

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