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Chemical Structure| 14924-53-9 Chemical Structure| 14924-53-9

Structure of 14924-53-9

Chemical Structure| 14924-53-9

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Product Details of [ 14924-53-9 ]

CAS No. :14924-53-9
Formula : C7H12O2
M.W : 128.17
SMILES Code : O=C(C1CCC1)OCC
MDL No. :MFCD00001321
InChI Key :SMVBADCAMQOTOV-UHFFFAOYSA-N
Pubchem ID :84700

Safety of [ 14924-53-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225
Precautionary Statements:P210-P403+P235
Class:3
UN#:3272
Packing Group:

Computational Chemistry of [ 14924-53-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.86
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 34.93
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.26
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

1.48
Log Po/w (WLOGP)?

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

1.35
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.

1.23
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

1.53
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.57

Water Solubility

Log S (ESOL):?

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

-1.37
Solubility 5.48 mg/ml ; 0.0428 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.

-1.64
Solubility 2.94 mg/ml ; 0.0229 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

-1.2
Solubility 8.09 mg/ml ; 0.0631 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.

-6.03 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)

1.57

Application In Synthesis of [ 14924-53-9 ]

* 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 [ 14924-53-9 ]

[ 14924-53-9 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 14924-53-9 ]
  • [ 74-88-4 ]
  • [ 65338-28-5 ]
YieldReaction ConditionsOperation in experiment
With lithium diisopropyl amide; In tetrahydrofuran; 1-Methyl-cyclobutanecarboxylic acid ethyl ester 1 was prepared from ethyl cyclobutanecarboxylate by the method described in J. Am. Chem. Soc, Vol. 103 No.2 1981 436-442.
With potassium hexamethylsilazane; In tetrahydrofuran; toluene; at -78 - 20℃; Step A; Ethyl 1-Methylcyclobutanecarboxylic Acid; To a solution of ethyl cyclobutanecarboxylate (1.0 g, 7.8 mmol) and methyl iodide (2.4 mL, 39 mmol) in 20 mL of anhydrous tetrahydrofuran at -78C was added potassium hexamethyldisilazide (0.5 M in toluene, 23 mL, 12 mmol), and the reaction was allowed to warm to room temperature overnight. After quenching with saturated ammonium chloride (10 mL), the resulting mixture was partitioned between water (100 mL) and ethyl acetate (100 mL). The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness to give the title compound, which was used without further purification. *H NMR (500 MHz, CD3OD): delta 4.12 (q,2H), 2.5-1.8 (m, 6H), 1.48 (s, 3H), 1.25 (t, 3H).
With lithium diisopropyl amide; In tetrahydrofuran; 1-Methyl-cyclobutanecarboxylic acid ethyl ester 1 was prepared from ethyl cyclobutanecarboxylate by the method described in J. Am. Chem. Soc, Vol. 103 No.2 1981 436-442.1-Methyl-cyclobutanecarboxylic acid ethyl ester 1 (1eq) was stirred under a nitrogen atmosphere at O0C in anhydrous THF. To this solution was added portionwise lithium aluminium hydride (1.5eq) and the suspension was stirred at room temperature for 3 hours. The reaction mixture was cooled on ice, treated with 1 M HCI (aq) and stirred at O0C 20 minutes. The solution was passed through a pad of celite and the filtrate extracted into diethyl ether. The organic phases were dried over MgSO4, filtered and concentrated in vacuo to give (i-methyl-cyclobutyl)-methanol, 2.Pyridinium chlorochromate (1.25eq) and the same weight of celite were taken up as a suspension in anhydrous dichloromethane. To this was added dropwise a solution of compound 2 (1eq) in anhydrous dichloromethane and the resulting heterogeneous mixture was stirred at room temperature for 3 hours. The reaction mixture was passed through a pad of silica, eluting with 19:1 isohexanes: ethyl acetate to give 1- methylcyclobutanecarboxaldehyde, 3.Compound 3 (1eq) was dissolved with stirring in anhydrous dichloromethane, and to this was added Boc-phosphoglycine trimethyl ester (0.5eq) and 1 ,8- EPO <DP n="120"/>diazabicyclo[5.4.0]undec-7-ene (1.2eq). The resulting solution was stirred at ambient temperature under nitrogen overnight. The reaction mixture was partitioned between dichloromethane and successively 1 M HCI (aq), sat. NaHCO3 (aq) and sat. NaCI (aq). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The resulting oil was purified by flash column chromatography, eluting with 1%methanol in dichloromethane to give 2-tert-butoxycarbonylamino-3-(1-methyl-cyclobutyl)-acrylic acid methyl ester, 4.Compound 4 was dissolved in anhydrous methanol and degassed with nitrogen. (+)- 1 ,2-bis (2S,5S)-diethylphosphonolanbenzene (cyclooctadiene)rhodium (I) triflate was added and degassing was continued for a further 10 minutes. The reaction was shaken under a hydrogen atmosphere (4 bar) for 48 hours. The solution was concentrated, in vacuo and purified by flash chromatography, eluting with dichloromethane, to give 2S- tert-butoxycarbonylamino-3-(1-methyl-cyclobutyl)-propionic acid methyl ester, 5.HPLC retention time 5.88min (monitored at 215 and 254 nm) HPLC using Synergy Max RP 80 mum 50x4.6mm column, 10?90% 6 min gradient of solution B (solution A = 0.1% TFA in water and solution B = 10% A in acetonitrile) at flow rate of 2ml/min.MS [M+H]+ 272.08 (20%) [M-Boc+H]+ 172.06 (100%)Electrospray ionisation, eluting with acetonitrile / ammonium formate buffer.1H NMR (400 MHz, CDCI35 4.83.79 (1 H, m) 4.33-4.27 (1 H, m) 3.71 (3H, s) 1.98-1.62 (8H, m) 1.42 (9H, s) 1.22 (3H, s)
With lithium diisopropyl amide; In tetrahydrofuran; at -78 - 20℃; Formation of ethyl 1-methylcyclobutanecarboxylate (111a)A solution of ethyl cyclobutanecarboxylate (20.0 g, 156.0 mmol) in THF (160 mL) was added dropwise to a cold (-78 C) solution of LDA (164 mmol of 2M solution) in THF (40 mL). The solution was warmed to 0 C and then cooled again to -40 C before the addition of iodomethane (10.2 mL, 163.8 mmol). The solution was slowly warmed to room temperature and stirred overnight. The reaction was quenched with an aqueous saturated solution of ammonium chloride and ether was added. The layers were separated and the aqueous layer was washed with ether. The combined organic layers were washed with IN HC1 then dried over MgS04. The product was purified by distillation: 1H NMR (400 MHz, MeOD) delta 4.20 - 4.05 (m, 2H), 2.57 - 2.33 (m, 2H), 2.08 - 1.94 (m, 1H), 1.94 - 1.77 (m, 3H), 1.40 (s, 3H), 1.27 (tt, J = 7.1, 1.5 Hz, 3H).
Formation of ethyl 1-methylcyclobutanecarboxylate (22a) A solution of ethyl cyclobutanecarboxylate (20.0 g, 156.0 mmol) in THF (160 mL) was added dropwise to a cold (-78 C) solution of LDA (164 mmol of 2M solution) in THF (40 mL). The solution was warmed to 0 C and then cooled again to -40 C before the addition of iodomethane (10.2 mL, 163.8 mmol). The solution was slowly warmed to room temperature and stirred overnight. The reaction was quenched with an aqueous saturated solution of ammonium chloride and ether was added. The layers were separated and the aqueous layer was washed with ether. The combined organic layers were washed with IN HC1 then dried over MgS04. The product was purified by distillation: XH NMR (400 MHz, MeOD) delta 4.20 - 4.05 (m, 2H), 2.57 - 2.33 (m, 2H), 2.08 - 1.94 (m, 1H), 1.94 - 1.77 (m, 3H), 1.40 (s, 3H), 1.27 (tt, J= 7.1, 1.5 Hz, 3H) ppm.

 

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