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Chemical Structure| 73415-84-6 Chemical Structure| 73415-84-6

Structure of 73415-84-6

Chemical Structure| 73415-84-6

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Product Details of [ 73415-84-6 ]

CAS No. :73415-84-6
Formula : C7H14ClNO2
M.W : 179.64
SMILES Code : O=C(O)CC1CCNCC1.[H]Cl
MDL No. :MFCD03414187
InChI Key :IYDUFJOXYMLYNM-UHFFFAOYSA-N
Pubchem ID :15565775

Safety of [ 73415-84-6 ]

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

Computational Chemistry of [ 73415-84-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 0
Fraction Csp3 0.86
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 49.1
TPSA ?

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

49.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

-1.44
Log Po/w (WLOGP)?

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

0.88
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.

0.69
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

0.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.18

Water Solubility

Log S (ESOL):?

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

0.09
Solubility 219.0 mg/ml ; 1.22 mol/l
Class?

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

Highly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

0.91
Solubility 1450.0 mg/ml ; 8.08 mol/l
Class?

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

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

-0.84
Solubility 25.8 mg/ml ; 0.144 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.

-8.42 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)

1.1

Application In Synthesis of [ 73415-84-6 ]

* 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 [ 73415-84-6 ]
  • Downstream synthetic route of [ 73415-84-6 ]

[ 73415-84-6 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 501-53-1 ]
  • [ 73415-84-6 ]
  • [ 63845-28-3 ]
YieldReaction ConditionsOperation in experiment
95% With sodium hydroxide In water at 20℃; for 16 h; Cooling with ice To prepare compound 2, a procedure published in DE 4304650 A1 was followed with modifications. 3000 mg (16.7 mmol) 2-(piperidin-4-yl) acetic acid hydrochloride (Iris Biotech, Marktredwitz, Germany) was dissolved in 46 ml of a 1 M solution of NaOH in water and cooled in an ice bath. 3350 μl benzyloxycarbonyl chloride (Cbz-Cl) (23.46 mmol, 4002 mg) were added dropwise over 5 min under stirring. The reaction mixture was allowed to warm to room temperature and stirred for 16 h. The aqueous solution was washed twice with 20 ml of diethyl ether/petroleum ether 4:1 and then acidified with 4 M HCl (aq.) to pH 1 . The product of the reaction was extracted with 3x 50 ml diisopropyl ether. The combined organic phases were dried with MgSO4 and evaporated under reduced pressure. Compound 2 was obtained as a colorless solid (4383 mg, 15.8 mmol, 95percent). 1H NMR (400 MHz, Chloroform-d) δ 7.40 - 7.27 (m, 5H), 5.13 (s, 2H), 4.18 (d, J = 13.3 Hz, 2H), 2.81 (t, J = 12.8 Hz, 2H), 2.29 (d, J = 7.0 Hz, 2H), 1.96 (tp, J = 11.2, 3.5 Hz, 1 H), 1.75 (d, J = 12.1 Hz, 2H), 1.30 - 1.09 (m, 2H)
60% With sodium hydroxide In water at 0 - 20℃; for 24 h; [00345] Intermediate 21: 2-(1 -Benzyloxycarbonyl-4-piperidyl)acetic acid [00346] 5 M NaOH (aq.) was added to a stirred solution of 2-piperidin-1-ium-4-ylacetic acidchloride (1 .OOg, 5.S7mmol) in water (4OmL) at 0 °C until pH 12 was reached. Benzyl chloroformate (0.79mL, 5.57mmol) was added dropwise to the solution. The mixture was stirred at roomtemperature for 24 hours and then the reaction mixture was extracted with Et20 (5OmL). Theaqueous fraction was acidified to pH 4 with 1 M HCI, then extracted with EtOAc (3 x 2OmL). The combined organic layers were dried over Na2SO4 and concentrated under vacuum to yield 2-Cl-Benzyloxycarbonyl-4-piperidyl)acetic acid (923mg, 3.33mmol, 60percent yield) as an off-white solid.1H NMR (DMSO-d6, 400MHz) O/ppm: 12.09 (1H, 5), 7.41-7.29 (5H, m), 5.06 (2H, 5), 4.21-4.04 (2H, m), 2.80-2.69 (2H, m), 2.15 (2H, d, J= 7.0Hz), 1.89-1.78 (1H, m), 1.73-1.64 (2H, m), 1.18-1.08 (2H,m).
References: [1] Patent: WO2014/125084, 2014, A1, . Location in patent: Page/Page column 33; 34.
[2] Patent: WO2016/51193, 2016, A1, . Location in patent: Paragraph 00344; 00345; 00346.
 

Historical Records

Technical Information

Categories

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[ 73415-84-6 ]

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Related Parent Nucleus of
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