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Chemical Structure| 1069-72-3 Chemical Structure| 1069-72-3

Structure of 1069-72-3

Chemical Structure| 1069-72-3

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Product Details of [ 1069-72-3 ]

CAS No. :1069-72-3
Formula : C6H15Br2N
M.W : 261.00
SMILES Code : CCN(CC)CCBr.[H]Br
English Name :2-Bromo-N,N-diethylethylamine Hydrobromide
MDL No. :MFCD00040376
InChI Key :HLMHCDKXKXBKQK-UHFFFAOYSA-N
Pubchem ID :70607

Safety of [ 1069-72-3 ]

Computational Chemistry of [ 1069-72-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 4
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 51.76
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.

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

2.73
Log Po/w (WLOGP)?

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

2.68
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.

2.54
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

1.32
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.85

Water Solubility

Log S (ESOL):?

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

-2.91
Solubility 0.318 mg/ml ; 0.00122 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.45
Solubility 0.921 mg/ml ; 0.00353 mol/l
Class?

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

-2.46
Solubility 0.903 mg/ml ; 0.00346 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.

-5.95 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

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<0.0
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)

2.18

Application In Synthesis of [ 1069-72-3 ]

* 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 [ 1069-72-3 ]

[ 1069-72-3 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 1069-72-3 ]
  • [ 330555-87-8 ]
  • [ 1646163-51-0 ]
YieldReaction ConditionsOperation in experiment
87% Stage #1: 7-hydroxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one With tetrabutyl-ammonium chloride; potassium carbonate In acetone for 0.333333h; Stage #2: 2-bromo-N,N-diethylethanamine hydrobromide In acetone for 4h; Reflux;
  • 2
  • [ 1215387-58-8 ]
  • [ 1069-72-3 ]
  • [ 2242824-75-3 ]
YieldReaction ConditionsOperation in experiment
66% Stage #1: 5-bromo-1H-pyrrolo[2,3-c]pyridine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.25h; Stage #2: 2-bromo-N,N-diethylethanamine hydrobromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 16h; 9 2-(5-Bromo-1H-pyrrolo[2,3-c]pyridin-1-yl)-N,N-diethylethanamine To a stirred suspension of 60% NaH (0.21 g, 8.88 mmol) in DMF (5 mL), 5-bromo-1H-pyrrolo[2,3-c]pyridine (0.7 g, 3.55 mmol) was added at °0 C and stirred for 15 min. Then, 2-bromo-N,N-diethylethylamine hydrobromide (1.1 g, 4.26 mmol) was added at °0 C. The reaction mixture was stirred at RT for 16 h and poured into ice cold water (50 mL), and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude compound was purified by flash column chromatography using 60% ethyl acetate in pet ether as an eluent to afford the title compound (0.7 g, 66%) as brown liquid. LC-MS (method 1): Rt =1.22 min; m/z = 296.24 (M+H+)
  • 3
  • [ 5913-13-3 ]
  • [ 1069-72-3 ]
  • [ 1568234-57-0 ]
YieldReaction ConditionsOperation in experiment
81% Stage #1: [(1R)-1-cyclohexylethyl]amine; 2-bromo-N,N-diethylethanamine hydrobromide With triethylamine In toluene for 72h; Reflux; Stage #2: With zinc(II) chloride In methanol; toluene for 12h; Stage #3: With sodium cyanide In dichloromethane at 20℃; for 4h; 2.3.2 Synthesis of LB 2-(Diethylamino)-ethylbromide hydrobromide (4.00g 15.32mmol) was refluxed with 2equiv. Et3N (3.10g 30.64mmol) and 1equiv. (R)-1-cyclohexylethanamine (1.94g 15.32mmol) in toluene (50mL) for 3days. After cooling ZnCl2 (2.27g, 15.32mmol) dissolving in MeOH 10mL was added to the solution and stirred for 12h. The white solid, Zn(II) complex, was filtered and dried in oven (70°C, 1h). Zn(II) complex (2.60g 7.17mmol) was dissolved in CH2Cl2 (20mL) and treated with 6equiv. NaCN (aq.) (2.11g, 43.0mmol) for 4h at the room temperature. The organic phase was dried with MgSO4. The solvent was eliminated by evaporation to get LB as a yellow oil (1.31g, 81%). Anal. Calc. for C14H30N2 (%): C, 74.27; H, 13.36; N, 12.37. Found: C, 73.90; H, 13.20; N, 12.40. 1H NMR (500MHz, CDCl3): δ 2.65-2.59 (m, 1H, CHCyH), 2.50-2.35 (m, 8H, NCH2), 1.63-1.51 (m, 6H, CyH), 1.26-1.20 (m, 1H, CyH), 1.14-0.97 (m, 4H, CyH), 0.95 (d, J=2.44Hz, 3H, CH3CHCyH), 0.92 (t, J=3.05Hz, 6H, NCH2CH3). 13C NMR (125MHz, CDCl3): δ 58.32 (1C, CHCyC), 52.98, 46.95 (2C, NCH2CH3), 45.40 (1C, CyC), 42.92, 29.96, 28.11, 26.65 (3C, CyC), 16.87 (1C, CH3CHCyC), 11.86 (2C, NCH2CH3). IR (oily liquid neat; cm-1): 2965 (w), 2922 (w), 2851 (w), 2805 (w), 1448 (m), 1371 (m), 1293 (m), 1202 (m), 1067 (m), 889 (m), 798 (m), 730 (m).
  • 4
  • [ 1069-72-3 ]
  • [ 136507-14-7 ]
  • [ 2377635-29-3 ]
YieldReaction ConditionsOperation in experiment
With sodium hydride In tetrahydrofuran at 0 - 20℃; for 16h;
  • 5
  • [ 1069-72-3 ]
  • [ 186390-77-2 ]
  • [ 2377635-13-5 ]
YieldReaction ConditionsOperation in experiment
54% With triethylamine In tetrahydrofuran for 24h; Reflux; VI.1 N,N-diethyl-2-(6-nitro-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-amine, (271). 6-nitro- 1,2,3,4-tetrahydroisoquinoline, 270 (300 mg, 1.68 mmols) and 2-(diethylamino)ethyl Bromide Hydrobromide (2.24 g, 8.42 mmols) were suspended in 25 ml of THF. Triethylamine (1.7 g, 16.84 mmols) was added in one portion. The mixture was stirred and heated under reflux conditions for 24 h. The solvent was evaporated under vacuum, the residue was dissolved in water (50 ml) and extracted with CH2CI2 (3 x 50 ml). The organic layer was dried over Na2S04, filtered, and the solvent removed under reduced pressure. The crude mixture was separated by flash column chromatography on basic alumina using CH2CI2, CH2Cl2:MeOH 98:2 for elution. Yield 250 mg (54 %). lH NMR (400 MHz, CDCl3) d 7.92 (d, J = 6.9 Hz, 2H), 7.16 (d, J = 9.1Hz, 1H), 3.80 (s, 2H), 3.14 - 3.07 (m, 4H), 2.97 (t, J = 5.8 Hz, 2H), 2.84 (t, J = 5.7 Hz, 2H), 1.37 (dd, J = 7.3, 3.9 Hz, 6H).
  • 6
  • [ 42523-29-5 ]
  • [ 1069-72-3 ]
  • [ 27591-97-5 ]
YieldReaction ConditionsOperation in experiment
1.6 g With potassium hydroxide In water; acetonitrile at 85℃; 5.V Example 5: Step V & VI: Preparation of Tilorone dihydrochloride (Formula g) 250-mL round bottom flask equipped with a stir bar was charged with 2,7-dihydoxy-9H- fluorenone (1g), 2-bromo-N, N-diethylethylamine hydrobromide (4.55 g) and KOH (2.26g), followed by the addition of 15mL acetonitrile and 3.2mL distilled water. The reaction was then stirred vigorously and heated to reflux for 20 h. After cooling to room temperature, the reaction mixture was poured into water and extracted with lfoO. The combined organic layers were dried over Na2SC>4, and the solvent evaporated under reduced pressure. The resulting residue was dried thoroughly to get the desired product as an orange gummy solid (1.6 g, 83 %). Which was dissolved in dry ether and added 2M ethereal HC1 solution drop by drop to obtain Tilorone dihydrochloride salt with >99% yield (1.88 g) and the orange product was recrystallized with anhydrous ethanol.
1.6 g With potassium hydroxide In water; acetonitrile at 85℃; 5.V Example 5: Step V & VI: Preparation of Tilorone dihydrochloride (Formula g) 250-mL round bottom flask equipped with a stir bar was charged with 2,7-dihydoxy-9H- fluorenone (1g), 2-bromo-N, N-diethylethylamine hydrobromide (4.55 g) and KOH (2.26g), followed by the addition of 15mL acetonitrile and 3.2mL distilled water. The reaction was then stirred vigorously and heated to reflux for 20 h. After cooling to room temperature, the reaction mixture was poured into water and extracted with lfoO. The combined organic layers were dried over Na2SC>4, and the solvent evaporated under reduced pressure. The resulting residue was dried thoroughly to get the desired product as an orange gummy solid (1.6 g, 83 %). Which was dissolved in dry ether and added 2M ethereal HC1 solution drop by drop to obtain Tilorone dihydrochloride salt with >99% yield (1.88 g) and the orange product was recrystallized with anhydrous ethanol.
 

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