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Chemical Structure| 39856-56-9 Chemical Structure| 39856-56-9

Structure of 39856-56-9

Chemical Structure| 39856-56-9

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Product Details of [ 39856-56-9 ]

CAS No. :39856-56-9
Formula : C7H9BrN2
M.W : 201.06
SMILES Code : CN(C)C1=CC=C(Br)N=C1
MDL No. :MFCD00100094
InChI Key :BORPINHDNLCKMO-UHFFFAOYSA-N
Pubchem ID :10976514

Safety of [ 39856-56-9 ]

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

Computational Chemistry of [ 39856-56-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.29
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 46.14
TPSA ?

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

16.13 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

2.0
Log Po/w (WLOGP)?

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

1.91
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.

1.25
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

1.56
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.75

Water Solubility

Log S (ESOL):?

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

-2.72
Solubility 0.379 mg/ml ; 0.00189 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.

-1.97
Solubility 2.18 mg/ml ; 0.0108 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

-2.99
Solubility 0.204 mg/ml ; 0.00102 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.

-6.11 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

0.0
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)

2.21

Application In Synthesis of [ 39856-56-9 ]

* 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 [ 39856-56-9 ]

[ 39856-56-9 ] Synthesis Path-Downstream   1~23

  • 2
  • [ 39856-56-9 ]
  • [ 63361-71-7 ]
  • 5
  • potassium trifluoro(1-tert-butoxycarbonyl-1H-indol-2-yl)boranuide [ No CAS ]
  • [ 39856-56-9 ]
  • [ 216480-88-5 ]
  • 6
  • [ 39856-56-9 ]
  • [ 214701-20-9 ]
  • 7
  • [ 39856-56-9 ]
  • [ 856014-55-6 ]
  • 8
  • [ 39856-56-9 ]
  • 5-(3-bromo-phenyl)-7-(5-dimethylamino-pyridin-2-yl)-pyrido[2,3-<i>d</i>]pyrimidin-4-ylamine [ No CAS ]
  • 9
  • [ 39856-56-9 ]
  • [ 144025-03-6 ]
  • [ 934477-86-8 ]
YieldReaction ConditionsOperation in experiment
3 g (80%) With potassium carbonate;Pd(PPh3)4; In 1,2-dimethoxyethane; dichloromethane; water; (2) Synthesis of 2-(2,4-difluorophenyl)-5-dimethylamino-pyridine <strong>[39856-56-9]2-bromo-5-dimethylaminopyridine</strong> (3.2 g, 16 mmol), 2,4-difluorophenylboronic acid (4.8 g, 30 mmol), K2CO3 (13 g, 94 mmol) and Pd(PPh3)4 (400 mg, 0.35 mmol) in a degassed mixture of DME/H2O (60/50 ml) were refluxed 24 hours under nitrogen. After being cooled to room temperature, the organic layer was separated and the aqueous phase extracted with EtOAc (100 ml). The combined organic fractions were washed with brine, dried over MgSO4 and evaporated to dryness. The crude compound was purified by column chromatography (SiO2, CH2Cl2 then CH2Cl2/MeOH: 97/3). The resulting brown solid was dissolved in CH2Cl2 and decolorized with charcoal. Filtration and evaporation of the solvent afford 3 g (80%) of the desired compound as a slightly yellow crystalline solid. 1H-NMR (CDCl3, 298K, 200 MHz, delta ppm) delta 3.03 (s, 6H), 6.9-7.1 (m, 3H), 7.60 (dd, J=2.5*9 Hz, 1H), 7.95 (m, 1H), 8.24 (d, J=2.5 Hz, 1H).
  • 10
  • [ 13534-97-9 ]
  • [ 39856-56-9 ]
YieldReaction ConditionsOperation in experiment
5.2 g (40%) With formaldehyd; aqueous KOH; HCO2H; In dichloromethane; water; Petroleum ether; (1) Synthesis of 2-bromo-5-dimethylaminopyridine 2-bromo-5-aminopyridine (11.7 g, 67.6 mmol) was added portionwise to HCO2H (20 ml) at 0 C. Formaldehyde (37% in water, 17 ml, 210 mmol) was then added and the mixture heated to reflux for hours. The reaction was then cooled to room temperature and an aqueous KOH solution (1N, ml) was added. The mixture was extracted with Et2O (3*100 ml) and the combined extract was dried over MgSO4, filtered and evaporated to dryness. The residual oil was purified by flash chromatography on silica (CH2Cl2). The yellowish solid was dissolved in the minimum volume of CH2Cl2, petroleum ether (150 ml) was added and the solution was stand in the fridge overnight. The white crystalline solid was filtered and washed with small portion of cold petroleum ether to afford 5.2 g (40%) of the desired compound as white crystalline solid. 1H-NMR (CDCl3, 298K, 200 MHz, delta ppm) delta 2.96 (s, 6H), 6.87 (dd, J=2.5*9 Hz, 1H), 7.25 (d, J=9 Hz, 1H), 7.84 (d, J=2.5 Hz, 1H).
  • 11
  • [ 39856-56-9 ]
  • 5-dimethylamino-2-carboxymethyl-pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
600 mg (46%) With n-butyllithium; sulfuric acid; In tetrahydrofuran; methanol; dichloromethane; water; Petroleum ether; (1) Synthesis of 5-dimethylamino-2-carboxymethyl-pyridine To a solution of <strong>[39856-56-9]2-bromo-5-dimethylaminopyridine</strong> (1.45 g, 7.2 mmol) in THF (100 ml) cooled to -78 C. was dropwise added nBuLi (1.6M, 6.3 ml, 10 mmol). The resulting orange solution was stirred at -78 C. for 40 minutes under nitrogen. CO2 (from dry-ice) was then bubbled into the solution during 3 hours while the temperature was allowed to reach room temperature. MeOH (2 ml) was then added and the solvent removed under vacuum. MeOH (100 ml) and concentrated H2SO4 (4 ml) were added and the resulting mixture refluxed overnight. The solvent was removed under vacuum and water (100 ml) was added. The mixture was neutralized with aqueous K2CO3 and extracted with CH2Cl2 (3*50 ml). The combined organic fractions were washed with brine, dried over MgSO4 and evaporated. The residue was purified by column chromatography (SiO2, CH2Cl2/MeOH: 95/5). The obtained orange oil was dissolved in CH2Cl2 (1 ml) and petroleum ether (100 ml) was added. The solution was stand in the fridge overnight. The formed precipitate was filtered and washed with small portions of cold petroleum ether to afford 600 mg (46%) of the desired compound as a slightly yellow solid. 1H-NMR (CDCl3, 298K, 200 MHz, delta ppm) delta 3.09 (s, 6H), 3.96 (s, 3H), 6.94 (dd, J=2.5*9 Hz, 1H), 7.99 (d, J=9 Hz, 1H), 8.17 (d, J=2.5 Hz, 1H). 13C-NMR (CDCl3, 298K, 50 MHz, delta ppm) delta 39.7, 52.2, 116.8, 126.2, 133.9, 134.9, 147.7, 166.1.
  • 13
  • [ 39856-56-9 ]
  • [ 1439378-79-6 ]
  • 14
  • 2-methyl-2-nitrosopropane dimer [ No CAS ]
  • [ 39856-56-9 ]
  • [ 1439378-71-8 ]
  • 18
  • [ 271-29-4 ]
  • [ 39856-56-9 ]
  • N,N-dimethyl-6-(1H-pyrrolo[2,3-c]pyridin-1-yl)pyridin-3-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% With copper(l) iodide; dimethylaminoacetic acid; caesium carbonate; In dimethyl sulfoxide; at 130℃; for 16h;Inert atmosphere; To a stirred solution of lH-pyrrolo[2,3-c]pyridine (100 mg, 0.84 mmol) in dimethyl sulfoxide (30 mL) were added <strong>[39856-56-9]6-bromo-N,N-dimethylpyridin-3-amine</strong> (204 mg, 1.01 mmol), dimethylglycine (52 mg, 0.51 mmol), copper(I) iodide (97 mg, 0.51 mmol) and cesium carbonate (1.1 g, 3.39 mmol) at ambient temperature. The resulting mixture was stirred for 16 hours at 130 C under nitrogen atmosphere. After cooling down to ambient temperature, the reaction mixture was quenched with water (80 mL) and extracted with ethyl acetate (3 x 80 mL). The combined organic layers was washed with brine (4 x 80 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography, eluted with 1-5% methanol in dichlorom ethane to afford N,N- dimethyl-6-(lH-pyrrolo[2,3-c]pyridin-l-yl)pyridin-3-amine as a light yellow solid: MS (ESI, m/z): 239.0 [M + 1]+; 1H MR (300 MHz, OMSO-d6) delta 9.47 (s, 1H), 8.22 (d, J= 5.1 Hz, 1H), 8.11-8.09 (m, 2H), 7.66 (s, 1H), 7.62-7.61 (m, 1H), 7.40-7.35 (m, 1H), 6.75 (d, J= 3.3 Hz, 1H), 3.02 (s, 6H).
  • 19
  • [ 13534-97-9 ]
  • [ 74-88-4 ]
  • [ 39856-56-9 ]
YieldReaction ConditionsOperation in experiment
72% To a solution of 6- bromopyridin-3 -amine (300 mg, 1.73 mmol) in tetrahydrofuran (30 ml) was added 1 M solution of lithium bis(trimethylsilyl)amide (3.46 mL, 3.46 mmol) in tetrahydrofuran over 5 min at - 78 C under nitrogen atmosphere. After stirring for 30 min at -78 C, iodomethane (566 mg, 3.99 mmol) was added. The resulting mixture was stirred for 1 hour at ambient temperature and then quenched by the addition of saturated aqueous solution of ammonium chloride (50 mL). The resulting mixture was extracted with ethyl acetate (3 x 50 mL). The combined organic layers was washed with brine (2 x 50 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography, eluted with 1-10% ethyl acetate in petroleum ether to afford 6-bromo- N,N-dimethylpyridin-3 -amine as a light yellow solid: MS (ESI, m/z): 201.0, 203.0 [M + 1]+.
  • 20
  • [ 13534-97-9 ]
  • [ 50-00-0 ]
  • [ 39856-56-9 ]
YieldReaction ConditionsOperation in experiment
0.43 g With formic acid; at 90℃; for 16h; Step a. To a solution of 6-bromopyridin-3 -amine (CAS Number 97-65-4) (1 g, 5.78 mmol) in formic acid (5 ml) was added para-formaldehyde (1.5 g, 1.5 eq w/w) at rt. The reaction mixture was heated at 90C for 16 hr. The resulting reaction mixture was poured into ice cold water, basified using solid sodium carbonate and extracted using EtOAc (30ml x 3). The organic layer was combined and dried over Na2S04 concentrated under reduced pressure. The obtained residue was purified using column chromatography (20% EtOAc in hexane) yielding 6-bromo-N, N-dimethylpyridin-3 -amine (0.43 g, 2.160 mmol). LCMS: Method C, 1.77 min, MS: ES+ 201.14. NMR (400 MHz, DMSO-d6) delta ppm 8.31-8.32 (d, 1 H), 7.84-7.85 (d, 1 H), 7.33-7.35 (d, 1 H), 2.91 (s, 6 H).
  • 21
  • [ 39856-56-9 ]
  • 6-bromo-2-iodo-N,N-dimethylpyridin-3-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.45 g With iodine; silver sulfate; In ethanol; at 20℃; for 2h; Step b. To a solution of <strong>[39856-56-9]6-bromo-N,N-dimethylpyridin-3-amine</strong> (1.2 g, 6.03 mmol) in ethanol (20 ml) were added silver sulphate (2.067 g, 6.63 mmol) and iodine (1.81 g, 7.24 mmol) at rt. The resulting reaction mixture was stirred at rt for 2 hr. The resulting reaction mixture was poured into water (50 ml), basified using solid sodium bicarbonate and extracted using EtOAc (50ml x 2). The organic layer was combined and washed with solution of sodium thiosulphate (50 ml), dried over Na2S04 and concentrated under reduced pressure. The obtained residue was purified using column chromatography (30% EtOAC in hexane) yielding 6-bromo-2-iodo-N,N-dimethylpyridin-3 -amine (1.45 g, 4.45 mmol). LCMS: Method C, 2.17 min, MS: ES+ 327.13.
  • 22
  • [ 39856-56-9 ]
  • 6-bromo-3-(dimethylamino)picolinonitrile [ No CAS ]
  • 23
  • [ 39856-56-9 ]
  • [ 131211-27-3 ]
  • [ 76-05-1 ]
  • di(1-adamantyl)-5-(N,N-dimethyl)-amino-2-pyridyl-phosphane trifluoroacetic acid [ No CAS ]
 

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Technical Information

Categories

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