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Structure of 828-52-4

Chemical Structure| 828-52-4

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Product Details of [ 828-52-4 ]

CAS No. :828-52-4
Formula : C10H16O3
M.W : 184.23
SMILES Code : OCC12CCC(CC1)(CC2)C(O)=O
MDL No. :MFCD09835291
InChI Key :CPVMAYNPSFMOGK-UHFFFAOYSA-N
Pubchem ID :301131

Safety of [ 828-52-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 828-52-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 0
Fraction Csp3 0.9
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 48.37
TPSA ?

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

57.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.53
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

0.7
Log Po/w (WLOGP)?

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

1.4
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.

1.31
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

1.66
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.32

Water Solubility

Log S (ESOL):?

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

-1.29
Solubility 9.42 mg/ml ; 0.0511 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.

-1.49
Solubility 6.02 mg/ml ; 0.0327 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

-1.28
Solubility 9.69 mg/ml ; 0.0526 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.

-6.93 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

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)

3.09

Application In Synthesis of [ 828-52-4 ]

* 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 [ 828-52-4 ]

[ 828-52-4 ] Synthesis Path-Downstream   1~15

  • 2
  • [ 828-52-4 ]
  • [ 98-59-9 ]
  • [ 2346-08-9 ]
  • 6
  • [ 828-52-4 ]
  • [ 100-39-0 ]
  • [ 340023-12-3 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 80℃; for 16.0h; Example 93 <strong>[828-52-4]4-Hydroxymethylbicyclo[2.2.2]octane-1-carboxylic acid</strong> benzyl ester (XVIII, Step O) <strong>[828-52-4]4-Hydroxymethylbicyclo[2.2.2]octane-1-carboxylic acid</strong> (XVII, Example 14, 24.8 g 135 mmol) is dissolved in DMF (950 ml). Anhydrous potassium carbonate (25 g, 181 mmol) is added to the solution slowly. Benzyl bromide (22 g, 12.94 mmol) is then added. The reaction mixture is heated at 80 for 16 hr. To the reaction mixture is added water (150 ml) and concentrated to give an oil, which was dissolved in ethyl acetate/hexane (5/1, 500 ml). The mixture is washed with saline (2*200 ml), dried over anhydrous sodium sulfate and concentrated to give the title compound, NMR (400 MHz, CDCl3) delta 7.39, 5.11, 3.28, 1.84 and 1.41.
  • 7
  • [ 94994-15-7 ]
  • [ 828-52-4 ]
YieldReaction ConditionsOperation in experiment
Example 92 4-Hydroxymethylbicyclo[2.2.2]octane-1-carboxylic acid (XVII, Step N) Lithium hydroxide (2 N, 250 ml) is added to a mixture of 4-hydroxymethyl-bicyclo[2.2.2]octane-1-carboxylic acid methyl ester (XVI, Example 91) in a mixture of THF (50 ml) and methanol (75 ml). The resulting reaction mixture is stirred at 20-25 for 16 hr, and then concentrated. The residue is diluted with water (30 ml) and washed with methylene chloride (100 ml) and ethyl acetate (100 ml). The aqueous layer is acidified with concentrated hydrochloric acid pH about 0 and extracted with ethyl acetate (3*250 ml). The ethyl acetate layers are combined and washed with saline (3*50 ml), dried over anhydrous sodium sulfate and concentrated to give the title compound, NMR (400 MHz, CDCl3) delta 3.09, 1.72 and 1.29.
  • 8
  • [ 18720-35-9 ]
  • [ 828-52-4 ]
YieldReaction ConditionsOperation in experiment
100% With sodium tetrahydroborate; In water; at 20℃; Sodium borohydride (5.8 g, 0.15 mol) was added portionwise to an aqueous solution (120 mL) of 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid (6.5 g, 0.03 mol).The reaction mixture was stirred at room temperature overnight.Ice water bath cooling,Dilute aqueous hydrochloric acid (1.0M) to adjust the pH to 2-3,Solid filter,The cake was washed with cold water (20 mL) and dried under reduced pressure to give compound 9.1(5.66 g, yield: 100%) as a white solid.
  • 9
  • [ 828-52-4 ]
  • C16H23NO3S [ No CAS ]
  • 10
  • [ 828-52-4 ]
  • C15H20N4 [ No CAS ]
  • 11
  • [ 828-52-4 ]
  • C15H22N2 [ No CAS ]
  • 12
  • [ 109-06-8 ]
  • [ 828-52-4 ]
  • C15H21NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
7% With ammonium persulfate; silver nitrate; In sulfuric acid; water; acetonitrile; at 80℃; for 1.0h; Aqueous ammonium persulfate solution (4.56 g, 0.02 mol, 10 mL) was added dropwise to compound 9.1 (3.68 g, 0.02 mol),2-methylpyridine (1.86 g, 0.02 mol)And silver nitrate (340 mg, 2.0 mmol) in 10% aqueous sulfuric acid (30 mL)And acetonitrile (40 mL).The reaction mixture is heated to 80 C,Stir for 1 hour,Then cool to ambient temperature,Use concentrated ammonia to adjust the pH to 8-9.Ethyl acetate (100 mL×2) was extracted and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure.The residue was purified by flash chromatography (petroleum ether/ethyl acetate = 1/1) to give compound 9.2 (200 mg, yield: 7%) as a pale yellow solid.
  • 13
  • [ 775304-79-5 ]
  • [ 828-52-4 ]
  • (methyl 4-(5-(4-hydroxymethyl)bicyclo[2.2.2]octan-1-yl)-1,2,4-oxadiazol-3-yl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 0 - 100℃; for 6.0h; To a 25 mL pear shaped flask were added <strong>[828-52-4]4-(hydroxymethyl)bicyclo[2.2.2]octane-1-carboxylic acid</strong> (160 mg, 0.85 mmol) (Kiesman W. F. et. al. WO 2001/034610) and BOP (38 mg, 0.85 mmol) in DMF (1 mL) followed by methyl (Z)-3-(N'-hydroxycarbamimidoyl)benzoate (Tung, R. D. WO 2016/073545) (150 mg, 0.77 mmol). To this mixture was added Et3N (0.32 mL, 2.3 mmol) at 0 C. The reaction mixture was stirred for 2 h at rt, and 4 h at 100 C. The reaction was cooled, the solvent was concentrated and the residue was dissolved in EtOAc (50 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography (24 g silica gel column; A=Hex, B=EtOAc; 15 min grad.; 0-30% B; flow rate=24 mL/min). The pure fractions were combined, concentrated and dried in vacuo to afford the title compound (120 mg, 45% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) delta=8.54 (t, J=1.5 Hz, 1H), 8.26 (dt, J=7.8, 1.5 Hz, 1H), 8.16 (dt, J=7.9, 1.6 Hz, 1H), 7.74 (t, J=7.7 Hz, 1H), 5.76 (s, 1H), 4.46 (t, J=5.5 Hz, 1H), 3.99-3.85 (m, 3H), 3.11 (d, J=5.4 Hz, 2H), 1.99 (d, J=7.8 Hz, 6H), 1.55-1.39 (m, 6H). MS (ESI) 343 (M+H).
  • 14
  • [ 828-52-4 ]
  • methyl 3-(5-(4-(((5-cyclopropyl-3-(2,6-dichloro phenyl)isoxazol-4-yl)methoxy)methyl)bicyclo[2.2.2]octan-1-yl)-1,2,4-oxadiazol-3-yl) benzoate [ No CAS ]
  • 15
  • [ 828-52-4 ]
  • 3-(5-(4-(((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)methyl)bicyclo[2.2.2]octan-1-yl)-1,2,4-oxadiazol-3-yl)benzoic acid [ No CAS ]
 

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