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Structure of 10472-24-9

Chemical Structure| 10472-24-9

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Product Details of [ 10472-24-9 ]

CAS No. :10472-24-9
Formula : C7H10O3
M.W : 142.15
SMILES Code : O=C(C1C(CCC1)=O)OC
MDL No. :MFCD00001411
InChI Key :PZBBESSUKAHBHD-UHFFFAOYSA-N
Pubchem ID :66328

Safety of [ 10472-24-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H315-H319-H335
Precautionary Statements:P305+P351+P338

Computational Chemistry of [ 10472-24-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.71
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 35.13
TPSA ?

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

43.37 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.47
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

0.52
Log Po/w (WLOGP)?

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

0.53
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

1.2
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.79

Water Solubility

Log S (ESOL):?

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

-0.92
Solubility 17.2 mg/ml ; 0.121 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.

-1.0
Solubility 14.2 mg/ml ; 0.0996 mol/l
Class?

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

Very 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

-0.98
Solubility 15.0 mg/ml ; 0.105 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

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.

-6.8 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

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)

2.05

Application In Synthesis of [ 10472-24-9 ]

* 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 [ 10472-24-9 ]

[ 10472-24-9 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 13304-62-6 ]
  • [ 10472-24-9 ]
  • 4-(1-benzyl-2,6-dioxo-piperidin-3-yl)-butyric acid methyl ester [ No CAS ]
  • 3
  • [ 1322091-22-4 ]
  • [ 10472-24-9 ]
  • methyl 1-(6-fluoro-3-p-tolyl-1H-isochromen-1-yl)-2-oxocyclopentanecarboxylate [ No CAS ]
  • C23H21FO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With diphenyl hydrogen phosphate; silver carbonate; In hexane; at 40℃; for 16.0h; General procedure: A dry single-necked flask was charged with 2-alkynylaldehyde 1 (0.4 mmol, 1 equiv), ketone 2 (0.8 mmol, 2 equiv), and diphenylphosphate (10 mg, 0.04 mmol, 10 mol %) in hexane (2.4 mL), and silver carbonate (2.75 mg 0.01 mmol, 2.5 mol%) was added. The mixture was heated to 40 C and stirred until the 2-alkynylaldehyde was completely consumed (progress of the reaction was monitored by TLC). The hexane was evaporated and the mixture was diluted in EtOAc (50 mL) and washed three times with water. The organic layer was dried over anhydrous Na2SO4 and filtered. After evaporating the EtOAc, the crude product was dissolved in dichloromethane and purified by column chromatography (silica gel; pentane/EtOAc, 96:4) to give pure 1H-isochromenes 3 as yellow oils or as colorless solids. In the case of phenylacetone and 2-phenylcyclohexanone as ketone nucleophiles, the crude product was directly purified by flash chromatography on silica gel.
  • 4
  • [ 10472-24-9 ]
  • [ 96558-73-5 ]
  • methyl 1-((2-bromo-3-chlorophenyl)diazenyl)-2-oxocyclopentane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% 2-Bromo-3-chloroaniline (600 g, 2.91 mol) and concentrated aqueous HCI (1500 mL, 49.4 mol) in water (1500 mL) were placed into a 4-necked RBF. The mixture was stirred overnight to give a solution. A solution of NaN02 (212 g, 3.07 mol) in water (720 mL) was added dropwise with stirring at 0-5 C. After 1.5 h, a solution of KOAc (4020 g, 40.9 mol) in water (6000 mL) and methyl 2-oxocyclopentane-1 -carboxylate (420 g, 2.95 mol) was added dropwise with stirring at 0-5 C. The resulting solution was stirred at 0-5 C for 0.5 h then for 2 h at RT. The solution was then extracted with 2 x10 L of DCM. The combined organic phases were washed with 1 x 5 L of brine. The solution was dried over anhydrous Na2S04 and concentrated to yield methyl 1-((2-bromo-3-chlorophenyl)diazenyl)-2-oxocyclopentane-1 -carboxylate (1070 g, 100%, 97 wt%).
100% 2-Bromo-3-chloroaniline (600 g, 2.91 mol) and concentrated aqueous HCI (1500 mL, 49.4 mol) in water (1500 mL) were placed into a 4-necked RBF. The mixture was stirred overnight to give a solution. A solution of NaN02 (212 g, 3.07 mol) in water (720 mL) was added dropwise with stirring at 0-5 C. After 1 .5 h, a solution of KOAc (4020 g, 40.9 mol) in water (6000 mL) and methyl 2-oxocyclopentane-1 -carboxylate (420 g, 2.95 mol) was added dropwise with stirring at 0-5 C. The resulting solution was stirred at 0-5 C for 0.5 h then for 2 h at RT. The solution was then extracted with 2 x10 L of DCM. The combined organic phases were washed with 1 x 5 L of brine. The solution was dried over anhydrous ^SC and concentrated to yield methyl 1 -((2-bromo-3-chlorophenyl)diazenyl)-2-oxocyclopentane-1 -carboxylate (1070 g, 100%, 97 wt%).
  • 5
  • [ 14381-51-2 ]
  • [ 10472-24-9 ]
  • C13H13BrO5 [ No CAS ]
  • C13H13BrO5 [ No CAS ]
  • 6
  • [ 67-56-1 ]
  • [ 10472-24-9 ]
  • [ 96558-73-5 ]
  • (E/Z)-dimethyl 2-(2-(2-bromo-3-chlorophenyl)hydrazono)hexanedioate [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% A mixture of <strong>[96558-73-5]2-bromo-3-chloroaniline</strong> (2.00 kg, 9.69 mol), hydrochloric acid (36 wt%, 4.85 L, 58.1 mol) and water (5 L) was stirred for 1 h. The resulting solution was cooled to 0 C, then a solution of NaNC>2 (702 g, 10.2 mol) in water (2.4 L) was gradually added over 1 h at 0-5C. After stirring for 1 h, methyl 2-oxocyclopentane-1 -carboxylate (1.38 kg, 9.69 mol) was gradually added at 0-5C. Then a solution of KOAc (13.3 kg, 136 mol) in water (20 L) was added gradually. The resulting solution was allowed to react for an additional 45 min at 0-5 C. The solution was then extracted three times with DCM (12 L per extraction). The combined organic extracts were washed with brine (10 L) and then charged to another reactor containing a solution of cone, sulfuric acid (4.75 kg, 48.5 mol) in MeOH (3.1 kg). The resulting solution was allowed to react for 3 h at 10-20 C. The solution was concentrated to about 8 L and then two cycles of adding MeOH (18 L per cycle) and distilling off solvent (18 L per cycle) under reduced pressure were completed. The resulting slurry was cooled to 0-10 C, stirred for 1 h and then filtered. The solid was washed with MeOH (2 x 2 L) and then dried in an oven under reduced pressure to give (E/Z)-dimethyl 2-(2-(2-bromo-3-chlorophenyl)hydrazono)hexanedioate, (0229) (Intermediate 1 , 3.3 kg, 94 wt%, 82%); m/z (ES+), [M+H]+ = 391. NMR (500 MHz, (0230) CHLOROFORM-d, 27C) delta 1.98 (m, 2H), 2.41 (t, 2H), 2.59 (t, 2H), 3.66 (s, 3H), 3.87 (s, 3H), 7.05 (dd, 1 H), 7.17 - 7.23 (m, 1 H), 7.49 (dd, 1 H), 12.48 (bs, 1 H).
  • 7
  • [ 27757-86-4 ]
  • [ 10472-24-9 ]
  • methyl 2-((thiophen-3-ylmethyl)amino)cyclopent-1-enecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With silica gel; In neat (no solvent); at 20℃; General procedure: To a mixture of 1 (621 muL, 0.711 g, 5 mmol) and SiO2 (7.11 g, 10 g per 1 g of 1), was added corresponding amines 2a-z (1.0 equiv) dropwise while stirring at rt. The resulting solid mixture was typically stirred for 1 h to overnight at rt. Upon complete consumption of starting material based on LCMS analysis, the solid mixture was purified by silica gel column chromatography to give the desired products 3a-z upon drying under vacuum (Table 1).
 

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