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Chemical Structure| 109-54-6 Chemical Structure| 109-54-6

Structure of 109-54-6

Chemical Structure| 109-54-6

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Product Citations

Product Citations

Lastowski, R Joseph ; Flores, Vincent J ; Souqui, Laurent ; Abelson, John R ; Girolami, Gregory S ;

Abstract: We describe the synthesis and characterization of three new square-planar compounds of stoichiometry M-[(CH2)3NMe2]2, where M = Ni, Pd, or Pt, each of which contains two chelating 3-dimethylamino-1-propyl ligands. The nickel(II) and palladium(II) compounds decompose above -78 and 0 °C, respectively, but the platinum(II) compound has a thermolysis onset temperature of 130 °C. The Pd and Pt complexes are dynamic in solution: they undergo ring inversion with small free energies of activation of ΔG⧧ = 7.9 ± 0.1 and 8.3 ± 0.1 kcal mol-1, respectively, at 298 K. The Pt complex sublimes at 40 °C and 5 mTorr. In benzene solution, the Pt compound thermolyzes primarily through β-hydrogen elimination; 80 ± 10% of the hydrogen atoms and 75 ± 5% of the carbon atoms from the precursor can be accounted for in the byproducts. The thermolysis of the Pt complex in C6D6 follows first-order kinetics, with an activation free energy ΔG⧧ of 29.9 ± 0.1 kcal mol−1 at 110 °C. Under CVD conditions, thin films grown of the Pt complex at 200 °C contain nanocrystalline Pt; analysis of the film growth byproducts suggest that the main decomposition pathway involves β-hydrogen elimination and reductive elimination steps, as seen in solution.

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Product Details of [ 109-54-6 ]

CAS No. :109-54-6
Formula : C5H12ClN
M.W : 121.61
SMILES Code : CN(C)CCCCl
MDL No. :MFCD00044496
InChI Key :NYYRRBOMNHUCLB-UHFFFAOYSA-N
Pubchem ID :66960

Safety of [ 109-54-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P422-P411-P280-P305+P351+P338

Computational Chemistry of [ 109-54-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 3
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 33.84
TPSA ?

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

3.24 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.04
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

1.21
Log Po/w (WLOGP)?

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

1.18
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.

1.53
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

0.87
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.37

Water Solubility

Log S (ESOL):?

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

-1.16
Solubility 8.45 mg/ml ; 0.0695 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.

-0.87
Solubility 16.2 mg/ml ; 0.133 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

-1.77
Solubility 2.05 mg/ml ; 0.0168 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

Low
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
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.

-6.18 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

2.0
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)

1.34

Application In Synthesis of [ 109-54-6 ]

* 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 [ 109-54-6 ]
  • Downstream synthetic route of [ 109-54-6 ]

[ 109-54-6 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 109-54-6 ]
  • [ 103146-26-5 ]
YieldReaction ConditionsOperation in experiment
76.9%
Stage #1: With iodine; magnesium In 2-methyltetrahydrofuran at 60℃; for 4.83333 h; Inert atmosphere
Stage #2: at -20℃; for 17.6167 h; Inert atmosphere
Stage #3: With hydrogen bromide In 2-methyltetrahydrofuran at 3℃; for 1 h;
Example 3 Preparation of N,N-dimethyl-3-chloromagnesiopropylamine Grignard reagent
2-methyl tetrahydrofuran as solvent:
Reaction process:
At room temperature, Mg (7.28 g, 300 mmol) and iodine granules (0.506 g, 2 mmol) were suspended in anhydrous 2-methyltetrahydrofuran (80 mL, moisture content: 0.016percent), the reaction mixture was purged with nitrogen for 6 times. The reaction mixture was heated to 60 deg. C and stirred for 15min, the mixture was orange-red.
3-chloro-N, N-dimethylpropylamine (CPA) (24.32 g, 200 mmol) was dissolved in anhydrous 2-methyltetrahydrofuran (120 mL) was added dropwise to the above reaction mixture, reaction liquid from milky white to gray-green, 110min dropwise additon was finished, reaction at 60 ° C for 3 h, the solution of N,N-dimethyl-3-chloromagnesiopropylamine Grignard reagent in 2-methyltetrahydrofuran was cooled to room temperature and was directly used in the next reaction.
Example 4 Preparation of 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile hydrobromide
2-methyl tetrahydrofuran as solvent:
Reaction process:
To a solution of the Grignard reagent of formula (III) (200 mL, 200 mmol) in anhydrous 2-methyltetrahydrofuran (541 mL) was added dropwise a solution of 2-methyltetrahydrofuran (541 mL) of formula (II) (54.30 g, 151.50 mmol), the solution was added dropwise over 97 min and the reaction mixture was stirred at -20 ° C for 16 h under nitrogen.
Reaction post-treatment:
Samples were quenched with saturated NH4Cl solution, and 2-methyltetrahydrofuran was analyzed by HPLC. The reaction mixture was allowed to warm to 0 ° C, and a saturated NH4Cl solution (120 mL) was added dropwise to the reaction mixture to quench the reaction mixture. The temperature of the reaction solution was maintained at 10 ° C or less, the white viscous solid was removed by suction filtration, the filtrate was cooled to 3 ° C and hydrogen bromide (30.30 g, 48percent, 179.70 mmol) was added dropwise to the filtrate, the reaction mixture was stirred at 3 ° C for 1 hour. The filtrate was concentrated under reduced pressure to remove 2-methyltetrahydrofuran. The reaction mixture was stirred at room temperature with CH2Cl2 (500 mL) and H2O (250 mL). The reaction mixture was cooled to room temperature, was added to the mixture, a white solid precipitated from the mixture, the reaction mixture was stirred at 15 ° C for 6 h, filtered, the white filter cake was washed with CH2Cl2 (3 x 80 mL) and dried in vacuo at 60 ° C for 16 h to give a white solid (49.33 g, yield: 76.9percent, based on 5-cyanophthalocyanine).
References: [1] Patent: CN105294496, 2016, A, . Location in patent: Paragraph 0120-0125; 0141- 0147; 0155-0167.
 

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Technical Information

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