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Structure of 6406-74-2

Chemical Structure| 6406-74-2

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Product Details of [ 6406-74-2 ]

CAS No. :6406-74-2
Formula : C9H14N2
M.W : 150.22
SMILES Code : NC1=CC=C(CN(C)C)C=C1
MDL No. :MFCD00035953
Boiling Point : No data available
InChI Key :NNCCQALFJIMRKB-UHFFFAOYSA-N
Pubchem ID :308051

Safety of [ 6406-74-2 ]

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

Computational Chemistry of [ 6406-74-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 2
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 48.32
TPSA ?

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

29.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.88
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

0.5
Log Po/w (WLOGP)?

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

1.19
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

1.0
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.22

Water Solubility

Log S (ESOL):?

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

-1.36
Solubility 6.59 mg/ml ; 0.0439 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.

-0.68
Solubility 31.1 mg/ml ; 0.207 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

-2.54
Solubility 0.438 mg/ml ; 0.00292 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

Yes
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.

-6.86 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.

1.0 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)

1.0

Application In Synthesis of [ 6406-74-2 ]

* 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 [ 6406-74-2 ]

[ 6406-74-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 15184-96-0 ]
  • [ 6406-74-2 ]
YieldReaction ConditionsOperation in experiment
85% With iron; In acetic acid; at 80℃; for 5h; To a solution of dimethyl-(4-nitro-benzyl)-amine (Ig, 5.55mmol) in acetic acid (10ml) was added activated iron powder (3g) and the reaction mixture was stirred for 5 hr at 800C. The reaction mixture was filtered; the filtrate diluted with water and neutralized with 10% sodium hydroxide solution. The product was extracted with ethyl acetate, the organic layer was dried and evaporated to give a residue. Purification by column chromatography using chloroform/methanol (98:2) to give 4-dimethylaminomethyl- phenylamine (0.7g, 85%)
78.2% With iron(III) chloride hexahydrate; pyrographite; hydrazine hydrate; In ethanol; at 65 - 78℃; for 5h; General procedure: A mixture of compounds 5a-e (0.05 mol) in ethanol was heated to 65 C, FeCl3·6H2O (2.8 g, 0.001 mol) and activated carbon (0.18 g, 0.015 mol) were added, and 80% hydrazine hydrate (25 g, 0.5 mol) was added drop wise at such a rate to keep the temperature below 70 C, the reaction was heated at reflux for 5 h and then cooled to room temperature and concentrated. Water (100 mL) was added, the reaction solution was extracted three times with DCM. The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated to obtain the compounds 6a-e.
78.2% With iron(III) chloride hexahydrate; hydrazine hydrate; In ethanol; for 5h; General procedure: A mixture of compounds 5 or 7a-c (0.05 mol) in ethanolwas heated to 65 C, FeCl3·6H2O (2.8 g, 1 mmol) and activatedcarbon (0.18 g, 15 mmol) were added, and 80% hydrazinehydrate (25 g, 0.5 mol) was added dropwise at such arate to keep the temperature below 70 C, the reaction washeated at reflux for 5 h and then cooled to room temperatureand concentrated. Water (100 mL) was added, the reactionsolution was extracted three times with CH2Cl2 (60 mL). Theorganic extracts were combined, dried over sodium sulfate,filtered, and concentrated to obtain the compounds 8a-d.
78.2% With iron(III) chloride; hydrazine hydrate; In ethanol; at 60 - 70℃; for 5h; General procedure: 1 (0.05 mol) was added to 90% ethanol (100 mL),The mixture was heated to 60 C with stirring, and ferric chloride (0.001 mol) and activated carbon (0.015 mol) were added. At 70 C, hydrazine hydrate (0.5 mol) was added dropwise, and the mixture was refluxed for 5 hours. After completion of the reaction, the mixture was filtered under suction, and the filtrate was concentrated. Water (200 mL), dichloromethane (100 mL×3)Concentrated to a colorless liquid orWhite solid 2a-c.
75% With hydrazine hydrate; iron(III) chloride hexahydrate; pyrographite; In ethanol; at 65 - 70℃; for 5h; A mixture of 3.5 g (19.4 mmol) of compound (b) in ethanol was heated to 65C. 0.83 g (0.39 mmol) of FeCl36H2O and 0.07 g (5.85 mmol) of activated carbon were added and 9.8 g (194 mmol) of 80% hydrazine hydrate was added dropwise at a rate maintaining the temperature below 70C .The reaction was heated at reflux for 5 hours, cooled to room temperature and concentrated. 500 ml of water was added and the reaction solution was extracted three times with DCM.The organic extracts were mixed, dried over sodium sulfate, and concentrated to obtain 3.2 g (75%) of a colorless cucumber compound (c).
palladium; In ethanol; REFERENCE EXAMPLE 15 In ethanol (100 ml) was dissolved dimethyl-4-nitrobenzylamine (20.7 g), and to the mixture was added dried 10% palladium on carbon (1.00 g). Under hydrogen atmosphere, the mixture was stirred at room temperature under atmospheric pressure for 20 hours. The palladium was filtered off, and the filtrate was concentrated. The residue was separated and purified with column chromatography (ethyl acetate) to give 4-aminobenzyl-dimethylamine (8.75 g) as pale yellow oil. 1 H NMR (200 MHz, CDCl3) delta: 2.21 (6H, s), 3.31 (2H, s), 3.53-3.70 (2H, br), 6.65 (2H, d, J=8.4 Hz), 7.08 (2H, d, J=8.4 Hz).
With hydrogen;palladium 10% on activated carbon; In methanol; under 3750.38 Torr; for 16h; 6.9 g (38.1 mmol) 4-nitro-dimethylbenzylamine are dissolved in 100 mL MeOH, combined with 1 g of palladium on activated charcoal (10 % Pd) and stirred for 16 h under a hydrogen atmosphere (5 bar) in the autoclave. After this time, total conversion can be detected (monitoring of reaction by HPLC). The catalyst is filtered off and all the volatile constituents are eliminated in vacuo. 6.8 g crude C-I are obtained, which is used without further purification in the syntheses of Examples 1, 2 and 6. MS-ESI+: 151 (M+H)+
Stannous chloride (28.1 g, 148 mmol) was added to a solution of Compound 4a2 (5.33 g, 29.6 mmol) in ethanol (200 mL) and heated to 60 C. Sodium borohydride (0.560 g, 14.8 mmol) in ethanol (80 mL) was added dropwise. Two hrs later the reaction mixture was added to ice water. The slurry was filtered through Celite 545 and the filtrate cake rinsed with ether. The collected liquors were brought to pH 11 with 1N NaOH and extracted with ether. The combined organic layers were washed with water, dried over MgSO4 and filtered. The dried organic solution was then reduced in vacuo to provide 4-dimethylaminomethyl-phenylamine Compound 4a which was used in the next step without further purification. MS 207 (MH+).
With hydrogenchloride; iron; acetic acid; In ethanol; water; for 0.75h;Reflux; PREPARATION 6: 4-((DIMETHYLAMINO)METHYL)ANILINE To a reaction flask was added N,N-dimethyl(4-nitrophenyl)methyamine (4.553 g). Anhydrous ethanol was added to dissolve N,N-dimethyl(4-nitrophenyl)methyamine. After adding acetic acid (5.2 mL), the mixture was mechanically stirred. To 1 N HCl (40 mL) was added iron powders (11.339g). The iron powders were immersed for 10 min and filtered by suction. The filter cake was washed with absolute ethanol and then added into the reaction flask. The mixture was warmed in an oil bath to reflux, and maintained under reflux until the reaction was completed (about 35 min). After the reaction was completed, the reaction solution was filtered by suction. The filter cake was washed with absolute ethanol. The filtrate was concentrated and then added into distilled water (100 mL). The pH of the mixture was adjusted with NaOH to 14. Lots of solids were precipitated. The solids were filtered by suction. The filtrate was extracted with dichloromethane (100 mL * 1), and the aqueous phase was discarded. To the organic phase was added distilled water (60 mL). The pH was adjusted with 2 N HCl to 2. The resultant product was mixed and stood to separate. The organic phase was discarded. The pH of the aqueous phase was adjusted with NaOH to 7. The mixture was extracted with dichloromethane (40 mL * 2) and the aqueous phase was discarded. The organic phase was washed with distilled water (40 mL * 1) once and the aqueous phase was discarded. The organic phase was directly concentrated to give the target compound.
With hydrogenchloride; iron; acetic acid; In ethanol; water; for 0.583333h;Reflux; To a reaction flask was added N,N-dimethyl(4-nitrophenyl)methyamine (4.553 g). Anhydrous ethanol was added to dissolve N,N-dimethyl(4-nitrophenyl)methyamine. After adding acetic acid (5.2 mL), the mixture was mechanically stirred. To 1 N HCl (40 mL) was added iron powders (11.339 g). The iron powders were immersed for 10 min and filtered by suction. The filter cake was washed with absolute ethanol and then added into the reaction flask. The mixture was warmed in an oil bath to reflux, and maintained under reflux until the reaction was completed (about 35 min). After the reaction was completed, the reaction solution was filtered by suction. The filter cake was washed with absolute ethanol. The filtrate was concentrated and then added into distilled water (100 mL). The pH of the mixture was adjusted with NaOH to 14. Lots of solids were precipitated. The solids were filtered by suction. The filtrate was extracted with dichloromethane (100 mL*1), and the aqueous phase was discarded. To the organic phase was added distilled water (60 mL). The pH was adjusted with 2 N HCl to 2. The resultant product was mixed and stood to separate. The organic phase was discarded. The pH of the aqueous phase was adjusted with NaOH to 7. The mixture was extracted with dichloromethane (40 mL*2) and the aqueous phase was discarded. The organic phase was washed with distilled water (40 mL*1) once and the aqueous phase was discarded. The organic phase was directly concentrated to give the target compound.

  • 2
  • [ 7647-01-0 ]
  • [ 15184-96-0 ]
  • SnCl2 [ No CAS ]
  • [ 6406-74-2 ]
  • 3
  • tin(II)chloride dihydrate [ No CAS ]
  • [ 15184-96-0 ]
  • [ 6406-74-2 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In ethanol; Reference Example 3 4-dimethylaminomethylaniline In 30 ml of ethanol, 2.93 g of N,N-dimethyl-4-nitrobenzylamine was dissolved, and 18.3 g of tin(II) chloride dihydrate was added to the solution, followed by stirring the resulting solution at 70 C. for 40 minutes. The reaction mixture was cooled to 0 C., and 100 ml of 2N aqueous sodium hydroxide solution was added to make the mixture basic. The resulting mixture was extracted with ethyl acetate (2*100 ml) and the organic layers were combined, dried and concentrated to obtain 2.46 g of unpurified captioned compound. NMR (90 MHz, CDCl3); delta 2.20 (6H, s), 3.39 (2H, br s), 3.62 (2H, br s, NH2), 6.63 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz).
 

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