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Chemical Structure| 1762-46-5 Chemical Structure| 1762-46-5

Structure of Diethyl bipy55'DC
CAS No.: 1762-46-5

Chemical Structure| 1762-46-5

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Product Details of [ 1762-46-5 ]

CAS No. :1762-46-5
Formula : C16H16N2O4
M.W : 300.31
SMILES Code : O=C(C1=CN=C(C2=NC=C(C(OCC)=O)C=C2)C=C1)OCC
MDL No. :MFCD11110569
InChI Key :IUNBUYCOAQHBMC-UHFFFAOYSA-N
Pubchem ID :12227215

Safety of [ 1762-46-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 1762-46-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 22
Num. arom. heavy atoms 12
Fraction Csp3 0.25
Num. rotatable bonds 7
Num. H-bond acceptors 6.0
Num. H-bond donors 0.0
Molar Refractivity 79.64
TPSA ?

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

78.38 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.26
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

1.92
Log Po/w (WLOGP)?

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

2.5
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.

1.16
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

3.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.37

Water Solubility

Log S (ESOL):?

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

-2.85
Solubility 0.421 mg/ml ; 0.0014 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.

-3.19
Solubility 0.194 mg/ml ; 0.000646 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

-5.12
Solubility 0.00227 mg/ml ; 0.00000757 mol/l
Class?

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

Moderately 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

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

Yes
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

Yes
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.

-6.77 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

0.0
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

1.0 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<0.0
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)

2.45

Application In Synthesis of [ 1762-46-5 ]

* 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 [ 1762-46-5 ]

[ 1762-46-5 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 64-17-5 ]
  • [ 1802-30-8 ]
  • [ 1762-46-5 ]
YieldReaction ConditionsOperation in experiment
77% at 0℃; for 24 h; Reflux Diethyl 2,2'-bipyridine-5,5'-dicarboxylate
Procedure:
Bipy55'DC (200 mg, 0.82 mmoles) and EtOH (13 mL) were added to a dried flask and stirred on ice.
Thionyl chloride (1.3 mL) was added dropwise on ice, after which the flask was fitted with a reflux condenser and heated at reflux.
After 24 hr, the reaction was cooled on ice and quenched by the dropwise addition of saturated Na2CO3 (20 mL).
The aqueous layer was extracted with CH2Cl2 (4*20 mL) and the combined organics were dried over Na2SO4(s), and concentrated under reduced pressure.
The crude product was then purified by chromatography on silica (3percent acetone in 1:1 DCM/hexanes) to afford the title compound (190 mg, 77percent) as a white solid. 1H NMR (500 MHz, CDCl3) δ 9.32 (dd, J=0.5, 2.0 Hz, 1H), 8.59 (dd, J=0.5, 8.5 Hz, 1H), 8.46 (dd, J=2.0, 8.5 Hz, 1H), 4.47 (q, J=7.5 Hz, 2H), 1.46 (t, J=7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 165.2, 158.3, 150.6, 138.1, 126.6, 121.3, 61.6, 14.3; HRMS (ESI) m/z 301.1193 [calc'd for C16H17N2O4 (M+H)+ 301.1183].
References: [1] Inorganic Chemistry, 2017, vol. 56, # 3, p. 1366 - 1374.
[2] Chemistry - A European Journal, 2012, vol. 18, # 23, p. 7030 - 7035.
[3] Dalton Transactions, 2016, vol. 45, # 3, p. 881 - 885.
[4] Chemical Communications, 2016, vol. 52, # 48, p. 7600 - 7603.
[5] Journal of the American Chemical Society, 2017, vol. 139, # 49, p. 17747 - 17750.
[6] Chemistry - A European Journal, 2018, vol. 24, # 10, p. 2457 - 2465.
[7] Chemistry - A European Journal, 2018, .
[8] Patent: US2016/280701, 2016, A1, . Location in patent: Paragraph 0300; 0301; 0302.
[9] Journal of the American Chemical Society, 2012, vol. 134, # 2, p. 968 - 978.
[10] Journal of Molecular Catalysis A: Chemical, 2010, vol. 331, # 1-2, p. 117 - 124.
[11] European Journal of Inorganic Chemistry, 1999, # 9, p. 1507 - 1521.
[12] Chemical Communications, 2009, # 41, p. 6237 - 6239.
[13] Journal of Heterocyclic Chemistry, 1977, vol. 14, p. 191,193.
[14] Journal of the American Chemical Society, 1982, vol. 104, # 26, p. 7519 - 7526.
[15] Dalton Transactions, 2008, # 28, p. 3701 - 3708.
[16] Physical Chemistry Chemical Physics, 2014, vol. 16, # 28, p. 14874 - 14881.
[17] Patent: CN106496113, 2017, A, . Location in patent: Paragraph 0059; 0060; 0066; 0067; 0073; 0074.
  • 2
  • [ 151917-39-4 ]
  • [ 1762-46-5 ]
YieldReaction ConditionsOperation in experiment
84% With palladium diacetate; potassium carbonate In N,N-dimethyl-formamide; isopropyl alcohol at 100℃; for 6 h; General procedure: A 100 mL round bottom flask was equipped with a magnetic stir bar and charged with the appropriate aryl iodide (1 equiv), K2CO3 (1.5 equiv), iPrOH (2 equiv), Pd(OAc)2 (5 mol percent), and a sufficient volume of DMF to make a 0.35 M solution. The reaction mixture was placed under nitrogen and heated to 100 C for 2–5 h until the starting material was consumed as judged by TLC analysis. The reaction mixture was cooled to room temperature and brine (40 mL) was added. The resulting mixture was transferred to a separatory funnel and extracted with EtOAc (3 × 75 mL). The organic layers were combined, washed with brine (1 × 75 mL), dried with Na2SO4, and the solvent was removed in vacuo to afford the crude product as a solid. The crude solid was purified by flash column chromatography or by recrystallization.
References: [1] Beilstein Journal of Organic Chemistry, 2015, vol. 11, p. 61 - 65.
  • 3
  • [ 614-18-6 ]
  • [ 1762-46-5 ]
References: [1] Journal of Organic Chemistry, 1997, vol. 62, # 9, p. 3013 - 3014.
[2] Journal of the American Chemical Society, 1987, vol. 109, # 22, p. 6619 - 6626.
[3] Angewandte Chemie, 1986, vol. 98, # 12, p. 1119 - 1121.
[4] Dalton Transactions, 2011, vol. 40, # 21, p. 5706 - 5710.
[5] Journal of the Chemical Society, 1956, p. 616,619.
[6] Journal of the Chemical Society, 1961, p. 1347,1349.
  • 4
  • [ 1762-34-1 ]
  • [ 1762-46-5 ]
References: [1] European Journal of Inorganic Chemistry, 1999, # 9, p. 1507 - 1521.
[2] Journal of Medicinal Chemistry, 1993, vol. 36, # 24, p. 3853 - 3858.
[3] Journal of the American Chemical Society, 1982, vol. 104, # 26, p. 7519 - 7526.
[4] Journal of the American Chemical Society, 2012, vol. 134, # 2, p. 968 - 978.
[5] Chemistry - A European Journal, 2012, vol. 18, # 23, p. 7030 - 7035.
[6] Chemistry - A European Journal, 2013, vol. 19, # 40, p. 13369 - 13375.
[7] Dalton Transactions, 2016, vol. 45, # 3, p. 881 - 885.
[8] Chemistry - A European Journal, 2018, .
  • 5
  • [ 1802-30-8 ]
  • [ 1762-46-5 ]
References: [1] Chemistry - A European Journal, 2013, vol. 19, # 40, p. 13369 - 13375.
  • 6
  • [ 64-17-5 ]
  • [ 1802-30-8 ]
  • [ 1762-46-5 ]
  • [ 105501-69-7 ]
References: [1] Journal of Medicinal Chemistry, 1993, vol. 36, # 24, p. 3853 - 3858.
[2] Journal of Medicinal Chemistry, 1993, vol. 36, # 24, p. 3853 - 3858.
  • 7
  • [ 108-99-6 ]
  • [ 1762-46-5 ]
References: [1] Journal of the American Chemical Society, 1982, vol. 104, # 26, p. 7519 - 7526.
  • 8
  • [ 1762-34-1 ]
  • [ 64-17-5 ]
  • [ 1762-46-5 ]
References: [1] Inorganic Chemistry, 2018, vol. 57, # 16, p. 9880 - 9891.
 

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