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Structure of 5653-40-7

Chemical Structure| 5653-40-7

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Product Details of [ 5653-40-7 ]

CAS No. :5653-40-7
Formula : C9H11NO4
M.W : 197.19
SMILES Code : C1=C(OC)C(=CC(=C1C(O)=O)N)OC
MDL No. :MFCD00011671
InChI Key :HJVAVGOPTDJYOJ-UHFFFAOYSA-N
Pubchem ID :79736

Safety of [ 5653-40-7 ]

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

Computational Chemistry of [ 5653-40-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 50.79
TPSA ?

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

81.78 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.27
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

1.26
Log Po/w (WLOGP)?

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

0.99
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.

-0.61
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

0.53
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.69

Water Solubility

Log S (ESOL):?

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

-1.98
Solubility 2.09 mg/ml ; 0.0106 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.

-2.58
Solubility 0.523 mg/ml ; 0.00265 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

-1.67
Solubility 4.2 mg/ml ; 0.0213 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.

-6.61 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.

0.56

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<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)

1.7

Application In Synthesis of [ 5653-40-7 ]

* 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 [ 5653-40-7 ]

[ 5653-40-7 ] Synthesis Path-Downstream   1~10

  • 2
  • [ 72605-86-8 ]
  • [ 5653-40-7 ]
  • [ 83350-78-1 ]
  • 3
  • [ 1055-23-8 ]
  • [ 5653-40-7 ]
  • [ 171002-51-0 ]
  • 4
  • [ 32315-10-9 ]
  • [ 5653-40-7 ]
  • [ 20197-92-6 ]
YieldReaction ConditionsOperation in experiment
86% In tetrahydrofuran; for 3h;Heating / reflux; 10.0 g (50.7 mmol) 2-Amino-4,5-dimethoxy-benzoic acid were dissolved in 150 ml tetrahydofuran. 6.52 g (22.0 mmol) triphosgene were added and the solution was boiled for 3 h. After equilibration to room temperature the reaction mixture was poured on a water/ice mixture. The residue was filtrated and rinsed with methanol. Yield: 8.7 g=86percent Grey powder
Reflux; Inert atmosphere; General procedure: To the solution of appropriate 2-aminobenzoic acid in dried THF or 1,4- dioxane was added triphosgene (0.35 eq). The mixture was stirred under reflux for 4-8 hrs. Then the solvent was removed in vacuo to give the isotaic anhydride as a solid in theoretical yield. 1H NMR indicated the product was of sufficient purity and was used in the next step without further purification.
  • 5
  • [ 5653-40-7 ]
  • NaOCN [ No CAS ]
  • [ 20197-92-6 ]
  • 6
  • [ 5653-40-7 ]
  • [ 20197-92-6 ]
  • 7
  • [ 501-53-1 ]
  • [ 5653-40-7 ]
  • [ 20197-92-6 ]
YieldReaction ConditionsOperation in experiment
96% 6,7-dimethoxy-2H-3,1-benzoxazine-2,4(1H)-dione, 13a; 2-amino-4,5-dimethoxybenzoic acid (25 g, 0.13 mole) was added to THF (400 ml), then benzyl chloroformate (54 ml, 0.38 mole) was added with very vigorous stirring. The mixture was refluxed overnight, evaporated to dryness and the residue was vacuum evaporated. Ether (425 ml) was poured on the residue, PBr3 (11.88 ml, 0.13 mole) was added and the mixture was refluxed for 48 h. The reaction mixture was filtered and washed with 3.x.150 ml of ether. The residue was taken up in ether and stirred for 1 h, then filtered, washed and dried. The reaction produced 27 g of the above product in the form of a white powder. Yield: 96percent. 1H NMR (DMSO-d6, 200 MHz): d 3.82 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 6.66 (s, 1H Ar), 7.27 (s, 1H Ar), 11.58 (s, 1H exchangeable NH).
  • 9
  • [ 943835-77-6 ]
  • [ 5653-40-7 ]
  • 13-fluoro-17-iodo-4,5-dimethoxy-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With iodine; sodium hydrogencarbonate; sodium sulfate; In acetonitrile; at 20℃; for 5h; General procedure: To a stirred mixture of 1aA (0.42 g, 2.0 mmol) and 2a (0.279 g, 2.0 mmol) in MeCN (15 mL) were added NaHCO3 (0.252 g, 3.0 mmol), I2 (0.762 g, 3.0 mmol) and anhydrous Na2SO4 (0.289 g, 2.0 mmol) at room temperature. The reaction was allowed to proceed at room temperature until complete consumption of starting material as monitored by TLC (ca. 5 h). After the reaction was complete, the mixture was washed with saturated Na2S2O3 solution, extracted with EtOAc (2×25 mL), dried over anhydrous Na2SO4, and evaporated in vacuum on a rotary evaporator to afford a residue. This residue was purified by column chromatography on silica gel using hexanes-EtOAc (70:30, v/v) as the eluent to furnish 0.85 g (94%) of 3aAa as a white solid. 4.2.13 13-Fluoro-17-iodo-4,5-dimethoxy-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one (3cAh) Yield: 80% (0.85 g from 0.45 g) as a gray solid, mp: 172-174 C; Rf=0.74 (CH2Cl2-MeOH, 9.5:0.5, v/v); IR (KBr) ν: 1713, 1586, 1232, 746 cm-1. 1H NMR (300 MHz, CDCl3): δ (ppm)=3.42 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 5.88 (s, 1H, ArH), 6.95 (s, 1H, CH), 7.11-7.15 (m, 2H, ArH), 7.27-7.40 (m, 5H, ArH), 7.43 (s, 1H, ArH), 7.76 (dd, 1H, J1=5.4 Hz, J2=8.3 Hz, ArH); 13C NMR (75 MHz, CDCl3): δ (ppm)=56.2, 56.3, 90.5, 107.6, 110.3, 114.7 (d, J=22.5 Hz), 115.2, 118.8 (d, J=22.5 Hz), 124.1 (d, J=33.0 Hz), 128.6, 129.2, 129.9, 130.5, 130.6, 132.2, 132.3, 133.4 (d, J=8.3 Hz), 138.8 (d, J=51.0 Hz), 141.9, 147.6, 152.9, 160.3, 163.1, 163.6. MS (ESI+): m/z=530.0. ESI-HRMS calculated for C24H17FINO4 [MH]+: 530.0265, found: 530.00268.
  • 10
  • [ 5653-40-7 ]
  • [ 574745-97-4 ]
 

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