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Structure of 4535-90-4

Chemical Structure| 4535-90-4

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Product Details of [ 4535-90-4 ]

CAS No. :4535-90-4
Formula : C3H9Cl2N
M.W : 130.02
SMILES Code : ClCCNC.[H]Cl
MDL No. :MFCD00050517
InChI Key :FGSHJLJPYBUBHO-UHFFFAOYSA-N
Pubchem ID :3028223

Safety of [ 4535-90-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 4535-90-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 2
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 31.1
TPSA ?

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

12.03 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

1.19
Log Po/w (WLOGP)?

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

1.25
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.

1.16
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

0.57
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.83

Water Solubility

Log S (ESOL):?

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

-1.26
Solubility 7.08 mg/ml ; 0.0545 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.

-1.04
Solubility 11.9 mg/ml ; 0.0915 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

-1.65
Solubility 2.89 mg/ml ; 0.0222 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.

-6.25 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

3.0
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)

1.42

Application In Synthesis of [ 4535-90-4 ]

* 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.

  • Upstream synthesis route of [ 4535-90-4 ]

[ 4535-90-4 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 109-83-1 ]
  • [ 4535-90-4 ]
YieldReaction ConditionsOperation in experiment
96% With thionyl chloride In dichloromethane EXAMPLE 2
N-Methyl-N-(2-chloroethyl)amine, hydrochloride salt
Hydrogen chloride was bubbled into a stirred solution of 2-(methylamino)ethanol (10 g, 133 mmol) in CH2 Cl2 (25 ml) until the mixture turned wet litmus paper red.
The mixture was cooled to 0° C., and thionyl chloride (15.82 g, 133 mmol) was added dropwise.
The mixture was allowed to stir overnight at room temperature.
The solvent was removed under reduced pressure to give product as a white solid (16.60 g, 96percent yield): mp 95°-100° C.; 1 H NMR (DMSO-d6) 4.00(t, 2H, J=6.28 Hz), 3.36(t, 2H, J=6.29 Hz), 2.81(s, 3H)ppm; IR (KBr) 3400, 2960, 2750, 2420, 1730, 1580, 1460, 1390, 1310, 1270, 1200, 1150, 1165, 1005, 990, 900, 860, 710 cm-1.
87% With thionyl chloride In chloroform at 0 - 50℃; for 17 h; Inert atmosphere To a solution of 2-(methylamino)ethanol (400 pL, 5.00 mmol, 1.0 equiv.) in chloroform (50 mL)was added, under argon at 0°C, thionyle chloride (1.09 mL, 15.0 mmol, 3.0 equiv.). After 17 h of stirring at 50°C, the solvent was concentrated until approximatively 10 mL, then diethyl ether (40 mL) was added to precipitate the compound which was collected on a fritglass, washed several times diethyl ether and dried with a vane pump during one night to afford compound A0219 (567 mg, 4.36 mmol) as a white solid in 87percent yield which was used in the next step without further purification. 1H NMR (400 MHz, MeOD) 5 3.91 (t, J = 5.4 Hz, 2H, CH2CI), 3.42 (t, J = 5.4 Hz, 2H, CH2N), 2.77 (s, 3H, CH3N). 13C NMR (100 MHz, MeOD) 551.46 (CH2N), 40.22 (CH2CI), 33.64 (CH3N).
References: [1] Journal of Medicinal Chemistry, 1995, vol. 38, # 14, p. 2672 - 2680.
[2] Patent: US5233031, 1993, A, .
[3] Chemical and Pharmaceutical Bulletin, 2002, vol. 50, # 7, p. 941 - 959.
[4] Journal of the Chemical Society. Dalton Transactions, 2001, # 8, p. 1306 - 1318.
[5] Journal of medicinal chemistry, 1992, vol. 35, # 17, p. 3246 - 3253.
[6] Patent: WO2015/140337, 2015, A1, . Location in patent: Page/Page column 33.
[7] Journal of Medicinal Chemistry, 1998, vol. 41, # 27, p. 5429 - 5444.
[8] Journal of the American Chemical Society, 2008, vol. 130, # 15, p. 5052 - 5053.
[9] Organometallics, 2012, vol. 31, # 21, p. 7427 - 7433,7.
[10] Chemische Berichte, 1905, vol. 38, p. 3132.
[11] Patent: WO2007/25889, 2007, A2, . Location in patent: Page/Page column 37; 39-40; 42.
[12] Journal of Polymer Science, Part A: Polymer Chemistry, 2014, vol. 52, # 5, p. 671 - 679.
  • 2
  • [ 62640-03-3 ]
  • [ 4535-90-4 ]
YieldReaction ConditionsOperation in experiment
80% With sulfuryl dichloride In chloroform at 0℃; for 3 h; Reflux To a stirred solution of 2-(methylamino)ethanol hydrochloride (29.7 g, 1.0 eq) in 150 mL CHCI3 was added sulfuryl dichloride (41 g, 1.3 eq) dropwise at 0 °C. After refluxing for 3 h, the reaction was cooled to rt. Then solvent was removed in vacuo, the residue was suspended in 100 mL solution (CH2C12: petroleum ether = 1 : 10), and filtered to give the desired product (28 g, 80percent). :H NMR (400 MHz, DMSO-c ) δ 9.24 (brs, 2H), 3.93(t, J= 6.0 Hz, 2H), 3.28 (t, J= 6.0 Hz, 2H), 2.56 (s, 3H).
References: [1] Patent: WO2013/97773, 2013, A1, . Location in patent: Paragraph 0236; 0312.
[2] Patent: EP1893695, 2009, B1, . Location in patent: Page/Page column 31.
  • 3
  • [ 1072-44-2 ]
  • [ 4535-90-4 ]
References: [1] Chemische Berichte, 1901, vol. 34, p. 3549.
 

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