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Chemical Structure| 173253-42-4 Chemical Structure| 173253-42-4

Structure of 173253-42-4

Chemical Structure| 173253-42-4

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Synonyms: 5-Bromo-6-chloropyrazin-2-amine

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Product Details of [ 173253-42-4 ]

CAS No. :173253-42-4
Formula : C4H3BrClN3
M.W : 208.44
SMILES Code : NC1=NC(=C(N=C1)Br)Cl
Synonyms :
5-Bromo-6-chloropyrazin-2-amine
MDL No. :MFCD09909642
InChI Key :CRVPQFAORCSDMH-UHFFFAOYSA-N
Pubchem ID :18180207

Safety of [ 173253-42-4 ]

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

Computational Chemistry of [ 173253-42-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 39.15
TPSA ?

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

51.8 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.32
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

1.42
Log Po/w (WLOGP)?

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

1.48
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.

0.37
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

1.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.25

Water Solubility

Log S (ESOL):?

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

-2.52
Solubility 0.629 mg/ml ; 0.00302 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.

-2.11
Solubility 1.61 mg/ml ; 0.00772 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

-2.77
Solubility 0.356 mg/ml ; 0.00171 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.

-6.56 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

0.0 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)

2.45

Application In Synthesis of [ 173253-42-4 ]

* 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.

  • Downstream synthetic route of [ 173253-42-4 ]

[ 173253-42-4 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 33332-28-4 ]
  • [ 173253-42-4 ]
YieldReaction ConditionsOperation in experiment
79% With N-Bromosuccinimide; In methanol; chloroform; acetonitrile; at 0 - 20℃; for 1h; To a solution of <strong>[33332-28-4]2-amino-6-chloropyrazine</strong> (5 g, 38.60 mmol) in a mixture of anhydrous chloroform (120 mL), anhydrous acetonitrile (12 mL) and anhydrous methanol (12 mL) was addedslowly, at 0CC, NBS (7.56 g, 42.45 mmol, 1.1 eq.) and the mixture was warmed to room temper-ature and continuously stirred for 1 h. The excess solvent was removed in vacuo and the obtained crude material (light brown solid) was purified by column chromatography (Hexane/DCM/MeOH = 50/50/0 then 0/1 00/0 then 0/95/5) to afford 5-bromo-6-chloropyrazin-2-amine(6.34 g, 30.42 mmol, 79percent) as white crystals. ESI-MS: 209.90 [M+H]+. 1 H NMR (300 MHz,CDCI3) 6 7.69 (s, 1 H), 4.78 (br s, 2H).
72% With N-Bromosuccinimide; In methanol; at 20℃; for 1h; 6-chloropyrazine-2-amine (10.4 g, 80 mmol) was dissolved in methanol (300 ml), and N-bromosuccinimide (15.6 g, 88 mmol) was added thereto while stirring at room temperature. After stirring for additional 60 minutes, the reaction product was concentrated under reduced pressure, followed by adding water so that the reaction product was extracted 3 times with ethyl acetate. The organic later was collected, dried over magnesium sulfate, and then concentrated under reduced pressure. Thereafter, the residue was purified on a silica gel column using chromatography. The title compound (12.0 g, 72percent) was obtained by eluting as a mixed solvent (3:1 v/v) of hexane and ethyl acetate. 1H NMR (500 MHz, CDCl3) delta 7.69 (s, 1H), 4.73 (s, 2H).
42% With N-Bromosuccinimide; In dichloromethane; at 0℃; for 1h; 2,6-Dichloropyrazine (2.89 g, 19.4 mmol) was stirred in aqueous NH3 (28percent, 10 ml.) and heated to 100°C in a sealed tube for 18 hours. The reaction mixture was cooled and the resultant precipitate was filtered. Trituration with water and then ether gave 6- chloropyrazin-2-amine as a white solid (2.28 g, 17.6 mmol, 91 percent yield). 1H NMR (d6-DMSO, 400 MHz) ? 6.9 (brs, 2H), 7.70 (d, J = 0.4, 1 H), 7.80 (d, J = 0.4, 1 H); LC-MS (ZQ, 6 minutes) Rt = 1.05 minutes; m/z (ESI+) 130 (M+H).6-Chloropyrazin-2-amine (2.50 g, 19.3 mmol) was stirred in CH2CI2 (60 ml.) at 0°C.A/-Bromosuccinimide (2.92 g, 16.4 mmol) was added slowly and the reaction mixture was stirred at 0°C for 60 minutes. The reaction mixture was filtered through celite and concentrated to give a brown oil. Purification by flash chromatography, eluting with 0-25percent EtOAc-hexanes, gave 5-bromo-6-chloropyrazin-2-amine as a yellow solid (1 .69 g, 8.16 mmol, 42percent yield). 1H NMR (de-DMSO, 400 MHz) ? 7.1 (brs, 2H), 7.65 (s, 1 H); LC-MS (ZQ, 4 minutes) Rt = 1.46 minutes; m/z (ESI-) 205 (M-H).A mixture of 5-bromo-6-chloropyrazin-2-amine (1 .00 g, 4.8 mmol), copper (I) iodide (914 mg, 4.8 mmol), 18-crown-6 (95 mg, 0.36 mmol) andtetrakis(triphenylphosphine)palladium (0) (83 mg, 0.072 mmol) was suspended in dry DMF (20 ml.) and a stream of nitrogen was passed through for 5 minutes. Potassium cyanide (312 mg, 4.8 mmol) was added and the mixture was stirred at room temperature for 30 minutes, then refluxed at 200°C for 3 hours. The mixture was cooled, diluted with EtOAc and absorbed onto silica gel (10 g). DMF was removed by evaporation. The product was purified by flash chromatography, eluting with 1 :1 EtOAc-hexanes, to yield 5- amino-3-chloropyrazine-2-carbonitrile as a yellow solid (607 mg, 3.93 mmol, 82percent yield). 1H NMR (d6 DMSO, 400 MHz) ? 7.87 (s, 1 H), 8.1 (brs, 2H); LC-MS (ZQ, 4 minutes) Rt = 1.20 minutes; m/z (ESI-) 153 (M-H).
42% With N-Bromosuccinimide; In dichloromethane; at 0℃; Synthesis 2-1 -B 5-bromo-6-chloropyrazin-2-amine 6-Chloropyrazin-2-amine (2.50 g, 19.3 mmol) was stirred in dichloromethane (60 mL) and cooled to O°C. N-Bromosuccinimide (2.92 g, 16.4 mmol) was added slowly and the reaction mixture was stirred at 0°C for 60 minutes. The reaction mixture was filtered through celite and concentrated to give a brown oil. Purification by flash chromatography, eluting with 0-25percent ethyl acetate-hexane, gave the title compound as a yellow solid (1.69 g, 8.16 mmol, 42percent). 1HMR (d6-DMSO, 400 MHz) delta 7.65 (s, 1H), 7.1 (br s, 2H). LC-MS (1) rt 1.46 min; m/z (ESI-) 205 (M-H).
With N-Bromosuccinimide; In chloroform; The starting 2-amino-5-bromo-6-chloropyrazine was obtained as follows: A solution of <strong>[33332-28-4]2-amino-6-chloropyrazine</strong> (5.0 g) and N-bromosuccinimide (13.9 g) in chloroform (200 ml) was heated under reflux for 2 hours. Insoluble material was removed by filtration and the filtrate was concentrated by evaporation. The residue was purified by flash chromatography on silica gel, eluding with dichloromethane, to give 2-amino-5-bromo-6-chloropyrazine (1.5 g); m.p. 120°-122° C.; mass spectrum (+ve CI): 208 (M+H)+.

  • 2
  • [ 128-08-5 ]
  • [ 33332-28-4 ]
  • [ 173253-42-4 ]
  • 2-amino-3-bromo-6-chloropyrazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
In chloroform; 4. 2-Chloro-3-bromo-6-aminopyrazine and 2-amino-3-bromo-6-chloropyrazine A solution of 2-chloro-6-aminopyrazine (20 g, 0.15 mole) in chloroform (1940 ml) was stirred at -5° C. to 0° C. N-Bromosuccinimide (27.58 g, 0.15 mole) was added in portions maintaining the temperature between -5 and 0° C. The mixture was warmed to room temperature and stirred for 3.50 hrs. The mixture was then washed with aqueous saturated sodium bicarbonate (1*300 ml), then water (1*500 ml), dried over anhydrous magnesium sulphate, filtered and the filtrate evaporated down in vacuo. The residue was purified by 'flash chromatography' using chloroform as the eluent. Yield of 2-chloro-3-bromo-6-aminopyrazine 13.89 g (43percent), M.p. 146-147° C. Yield of 2-amino-3-bromo-6-chloropyrazine 4.90 g (15percent), M.p. 124-125° C.
  • 3
  • [ 33332-28-4 ]
  • [ 173253-42-4 ]
  • 2-amino-3-bromo-6-chloropyrazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With N-Bromosuccinimide; In chloroform; at 0 - 20℃; Preparation of 3-bromo-6-chloropyrazin-2 -amine (B-10-3).-10-2 B-10-3 B-10-3bTo a solution of compound B-10-2 (110 g, 0.85 mol) in CHCI3 (1.5 L) was added N-bromo-succinimide (151.3 g, 0.85 mol) portionwise at O0C under N2 atmosphere. After the addition, the reaction mixture was warmed to room temperature and stirred overnight. TLC (petroleum ether/EtOAc 3:1 ) indicated most of compound B-10-2 was consumed. The reaction mixture was washed with saturated Na2CO3 (1 L x 3), H2O (1 L x 3) and saturated aqueous NaCI (1 L) in sequence, dried over Na2SO4 and concentrated in vacuo. The residue was purified via column chromatography (silica gel, EtOAc/hexane 1 :20) to yield pure B-10-3b (35 g) and pure compound B-10-3 (45 g, 28percent) as a yellow solid.
 

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Technical Information

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