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Chemical Structure| 36052-24-1 Chemical Structure| 36052-24-1

Structure of 36052-24-1

Chemical Structure| 36052-24-1

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Product Details of [ 36052-24-1 ]

CAS No. :36052-24-1
Formula : C7H8N2O2
M.W : 152.15
SMILES Code : O=C(OC)C1=CN=C(N)C=C1
MDL No. :MFCD00797844
InChI Key :JACPDLJUQLKABC-UHFFFAOYSA-N
Pubchem ID :737487

Safety of [ 36052-24-1 ]

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

Computational Chemistry of [ 36052-24-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 39.92
TPSA ?

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

65.21 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.44
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

1.68
Log Po/w (WLOGP)?

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

0.46
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.

0.15
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

0.47
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.84

Water Solubility

Log S (ESOL):?

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

-2.11
Solubility 1.17 mg/ml ; 0.0077 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.

-2.66
Solubility 0.33 mg/ml ; 0.00217 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

-1.73
Solubility 2.87 mg/ml ; 0.0188 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.

-6.04 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

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)

1.54

Application In Synthesis of [ 36052-24-1 ]

* 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 [ 36052-24-1 ]

[ 36052-24-1 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 36052-24-1 ]
  • [ 119999-22-3 ]
  • methyl 6-((3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino)nicotinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 120 - 125℃; for 22h;Inert atmosphere; a. Methyl 6-((3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino)nicotinate (79). To a solution of 77 (1.1216 g, 3.99 mmol), 78(0.5910 g, 3.88 mmol), CsCO3 (3.1158 g, 9.58 mmol), rac-B1NAP (0.1856 g, 0.30 mmol) in toluene (4.5 mL) in a 100 mL round-bottomed flask was added Pd2(dba)3 (0.1755 g, 0.19 mmol). The solution was sparged with nitrogen for 5 mm., then a reflux condenser was fitted to the flask, the atmosphere was evacuated and back-filled with nitrogen (three times), and the reaction was heated to reflux with stirring in an oil bath (125-120 C) for 22h. After cooling the reaction to room temperature, excess cesium carbonate and other solid particulates were filtered and washed with ethyl acetate, and the organic filtrate was concentrated in vacuo to give a crude product that was purified by column chromatography (150 mE Si02, 6.5% ethyl acetate:hexanes to 10% ethyl acetate: hexanes) to give 79 (0.5072 g, 37%) as a crystalline solid, m.p. 169-175.8 C: ?H NMR (400 MHz, CDC13) 6 8.79 (dd, J= 2.4, 0.8, JH), 8.00 (dd, J= 8.8, 2.0, 1H), 7.25 (s, 1H), 7.18 (s, 1H), 7.05 (brs, 1H), 6.49 (dd,J 8.8, 0.8, 1H), 3.87 (s, 3H), 2.20 (s, 3H),1.68 (s, 4H), 1.29 (s, 6H), 1.25 (s, 6H); ?3C NMR (100.6 MHz, CDC13) 6 166.1, 160.0, 151.3, 143.8,143.0, 138.9, 134.1, 130.3, 129.1, 123.1, 116.1, 105.5, 51.7, 35.0, 34.9, 34.0, 33.9, 31.8, 31.8, 17.6; IR (neat) 2961, 1722, 1605, 1399, 1273 cm?; ES-MS (M+Na)+ calcd for C22H28N2O2Na 375.2048, found 375.2050.
  • 2
  • [ 36052-24-1 ]
  • [ 351410-62-3 ]
  • 6-[(5-fluoro-2-methoxypyridin-3-ylmethyl)amino]nicotinic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
832 mg With triethylsilane; trifluoroacetic acid; In acetonitrile; for 3h;Reflux; In a round bottom flask, 6-amino-nicotinic acid methyl ester (90, 0.678 g, 4.46 mmol) was combined with <strong>[351410-62-3]5-fluoro-2-methoxy-pyridine-3-carbaldehyde</strong> (37, 0.532 g, 3.43 mmol), 10.6 mL of acetonitrile, trifluoroacetic acid (1.32 mL, 17.1 mmol) and triethylsilane (3.29 mL, 20.6 mol). The reaction was heated to reflux for 3 hours, then poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (91, 832 mg). MS (ESI) [M+H+]+=292.4.
  • 3
  • [ 36052-24-1 ]
  • [ 26346-85-0 ]
  • [ 1051397-08-0 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In ethanol; at 70℃; General procedure: Sodium carbonate (0.96 g, 9.06 mmol) was added after dissolving 6-aminonicotinate (1.5 g, 9.96 mmol) and G (2.2 g, 9.06 mmol) inethanol. The mixture was stirred at 70 C for 6 to 8 h. The solvent wasremoved under reduced pressure. The residue was added with waterand ethyl acetate to dissolve. The extracts were combined and washedby saturated brine. The organic phase was concentrated in vacuo afterdrying over anhydrous sodium sulfate and purified by column chromatographyto acquire expected compound H as a yellow solid. Yield1.13 g, 42.16%. 1H NMR (300 MHz, DMSO) δ 9.48 (s, 1H), 8.61 (s, 1H),8.33 (d, J = 9.6 Hz, 1H), 7.63 (s, 2H), 7.33 (t, J = 9.1 Hz, 1H), 7.24 -6.89 (m, 2H), 4.22 (q, J=7.5 Hz, 2H), 3.91 (s, 3H), 1.56 (t, J=7.4 Hz,3H). 13C NMR (75 MHz, DMSO-d6) δ 165.56, 156.44, 144.31, 132.01,129.58, 128.67, 124.23, 120.93, 116.26, 115.29, 114.45, 112.63,64.21, 52.73, 15.26.
 

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Technical Information

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