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Chemical Structure| 7752-82-1 Chemical Structure| 7752-82-1

Structure of 7752-82-1

Chemical Structure| 7752-82-1

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Product Details of [ 7752-82-1 ]

CAS No. :7752-82-1
Formula : C4H4BrN3
M.W : 174.00
SMILES Code : C1=C(C=NC(=N1)N)Br
MDL No. :MFCD00012341
InChI Key :UHRHPPKWXSNZLR-UHFFFAOYSA-N
Pubchem ID :231310

Safety of [ 7752-82-1 ]

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

Computational Chemistry of [ 7752-82-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
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 34.14
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.

1.26
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

0.55
Log Po/w (WLOGP)?

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

0.83
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.

0.15
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

1.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.76

Water Solubility

Log S (ESOL):?

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

-1.82
Solubility 2.63 mg/ml ; 0.0151 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.

-1.21
Solubility 10.7 mg/ml ; 0.0617 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

-2.14
Solubility 1.25 mg/ml ; 0.00721 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.

-6.97 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

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)

1.52

Application In Synthesis of [ 7752-82-1 ]

* 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 [ 7752-82-1 ]

[ 7752-82-1 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 107-20-0 ]
  • [ 7752-82-1 ]
  • [ 865156-68-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In water; at 25℃; for 24h; c) 6-Bromo-imidazo[1,2-a]pyrimidine; 50 mmol of 5-bromo-pyrimidin-2-ylamine are dissolved in 200 mi of saturated aqueous sodium hydrogencarbonate solution. 55 mmol of chloroacetaldehyde are added to the reaction mixture and the mixture is stirred for 24 hours at 25C. The mixture is extracted with ethyl acetate (3x300 mi) and the combined extracts are dried over sodium sulphate and evaporated under reduced pressure. Flash chromatography (Si02 60F) of the residue provides the title compound which is identified on the basis of its Rf-value.
In ethanol; water; at 20℃; for 16h;Heating / reflux; Example 9; 211 212 213Part A:To compound 211 (1.00 g, 5.74 mmol) in ethanol (100 ml_) was added chloroacetaldehyde (50 wt% solution in water, 7.34 ml_, 57.5 mmol) at room temperature. The reaction mixture was heated at reflux for 16 hours at which time LC- MS analysis indicated that the reaction was complete. The reaction mixture was concentrated under vacuum. The residue was taken back up in ethyl acetate and saturated sodium bicarbonate. The organic and aqueous layers were separated. The organic layer was washed with brine, dried over anh. sodium sulfate and concentrated to afford compound 212 as a beige solid. 1H NMR (400 MHz, DMSO-d6) delta 9.32 (d, 1 H), 8.56 (d, 1 H), 7.85 (d, 1 H), 7.74 (d, 1 H).
With sodium hydrogencarbonate; In water; at 25℃; for 24h; c) 6-Bromo-imidazof1w2-alPyrimidine; 50 mmol of 5-bromo-pyrimidin-2-ylamine are dissolved in 200 mi of saturated aqueous sodium hydrogencarbonate solution. 55 mmol of chloroacetaldehyde are added to the reaction mixture and the mixture is stirred for 24 hours at 25C. The mixture is extracted with ethyl acetate (3x300 ml) and the combined extracts are dried over sodium sulphate and evaporated under reduced pressure. Flash chromatography (SiO2 60F) of the residue provides the title compound which is identified on the basis of its Rf-value
  • 2
  • [ 850568-54-6 ]
  • [ 7752-82-1 ]
  • [ 1029715-16-9 ]
YieldReaction ConditionsOperation in experiment
86.6% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 120℃; for 3h; Sodium carbonate (0.636 g, 6.0 mmol) in water (2.0 mL) was added to a mixture of 5- bromopyrimidin-2-amine (0.348 g, 2.0 mmol), <strong>[850568-54-6][4-(tert-butoxycarbonyl)phenyl]boronic acid</strong> (0.533 g, 2.4 mmol) and tetrakis(triphenylphosphine)palladium (69 mg, 0.06 mmol) in ethanol (3 mL) and toluene (3 mL). The mixture was heated at 120 0C for 3 h. After cooling to RT, the mixture was diluted with EtOAc and washed with water and brine. The organic layer was dried over Na2SOzI, filtered and concentrated under reduced pressure to afford the desired product (470 mg, 86.6percent) which was directly used in next step. LCMS: (M+H) = 272.1.
  • 3
  • [ 7752-82-1 ]
  • [ 148493-34-9 ]
  • [ 1031439-19-6 ]
  • 4
  • [ 7752-82-1 ]
  • [ 2032-35-1 ]
  • [ 865156-68-9 ]
YieldReaction ConditionsOperation in experiment
20 g Under ice cooling, water (20 mL), hydrobromic acid (content 48%, 20 mL) and bromoacetaldehyde diethyl acetal (45 mL) was added to, and stirred for 1 hour 30 minutes at room temperature. After stirring the reaction solution with ice-cold vigorously was added sodium hydrogen carbonate (31 g), the reaction solution was filtered. To the filtrate, ethanol (122 ml) and 2-amino-5-bromopyrimidine (21 g) was added and stirred for 35 min at 85 C. To the reaction solution was ice-cooled, water (244 mL) was added, was neutralized with sodium hydroxide solution of 4M, and stirred for 30 minutes. Collected by filtration resulting suspension, water (60 mL), followed by n- washed with hexane (60 mL), to give after drying the title compound (20 g) as a solid.
  • 5
  • [ 7752-82-1 ]
  • [ 437-86-5 ]
  • [ 1538605-30-9 ]
YieldReaction ConditionsOperation in experiment
52% In tetrahydrofuran; at 0℃; for 3h;Inert atmosphere; Sodium hydride (1.37g, 34.28 mmol) was slowly added to a stirred solution of 5- bromopyrimidin-2-amine (5g, 28.57 mmol) in THF (lOmL) at 0 °C under argon atmosphere followed by the addition of 2-fluoro-l-methyl-3-nitrobenzene (4.87g, 31.42 mmol). The reaction mass was stirred for 3h at room temperature. Cooled the reaction mass to 0 °C and quenched the reaction mass with ethyl acetate and water. Separated the organic layer and the organic layer was washed with brine, dried over Na2S04, filtered and concentrated under vacuum. The crude residue was purified by column chromatography on 60-120 silica gel by eluting with 0-10percent ethyl acetate - hexane to afford the desired title compound (4.5g, 52percent); LCMS: m/z = 309.0 (M+H)+.
 

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Technical Information

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