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Chemical Structure| 875781-41-2 Chemical Structure| 875781-41-2

Structure of 875781-41-2

Chemical Structure| 875781-41-2

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Product Details of [ 875781-41-2 ]

CAS No. :875781-41-2
Formula : C9H12BrN3Si
M.W : 270.20
SMILES Code : C[Si](C)(C)C#CC1=C(N)N=CC(Br)=N1
MDL No. :MFCD16660032
Boiling Point : No data available
InChI Key :LQJGZEFWBXJKJI-UHFFFAOYSA-N
Pubchem ID :53393189

Safety of [ 875781-41-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 875781-41-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 64.36
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.

2.6
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

2.69
Log Po/w (WLOGP)?

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

2.14
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.

1.29
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

0.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.9

Water Solubility

Log S (ESOL):?

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

-3.53
Solubility 0.0803 mg/ml ; 0.000297 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.

-3.43
Solubility 0.1 mg/ml ; 0.000371 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

-3.5
Solubility 0.0864 mg/ml ; 0.00032 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.

-6.04 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

2.0 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)

3.34

Application In Synthesis of [ 875781-41-2 ]

* 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 [ 875781-41-2 ]

[ 875781-41-2 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 875781-41-2 ]
  • [ 98-59-9 ]
  • [ 1201186-54-0 ]
YieldReaction ConditionsOperation in experiment
52% To a solution of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (3.00 g, 11.1 mmol) in DMF (60 mL) at about 0 C. was added NaH (60% dispersion in mineral oil, 0.577 g, 14.4 mmol) in three portions. After about 15 min, p-toluenesulfonyl chloride (2.75 g, 14.4 mmol) was added and the reaction was allowed to warm slowly to ambient temperature. After about 16 h, the reaction mixture was poured onto ice-cold water (120 mL) and the precipitate was collected by vacuum filtration. The crude solid was dissolved in DCM (15 mL) and purified by silica gel chromatography eluting with DCM. The product-containing fractions were concentrated under reduced pressure to give 2-bromo-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (2.16 g, 52%): LC/MS (Table 2, Method d) Rt=1.58 min; MS m/z: 352/354 (M+H)+.
39.2% To a 0 oc solution of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (1.22 g,4.52 mmol) in anhydrous DMF (10 mL) was added sodium hydride (253 mg, 6.33 mmol, 60 %).The mixture was stirred at 0 oc for 15 min, then paratoluensulfonyl chloride (865 mg, 4.51mmol) was added into the mixture. The resulting mixture was warmed to rt and stirred for 3 h.To the reaction mixture was added ice-water (40 mL) to quench the reaction, and the resultingmixture was extracted with ethyl acetate (30 mL x 3). The combined organic layers were washedwith saturated brine (60 mL), dried over anhydrous sodium sulfate and filtered. The filtrate wasconcentrated in vacuo and the residue was purified by silica gel column chromatography(PE/EtOAc (v/v) = 1011) to give the title compound as a yellow solid (624 mg, 39.2 %).
39.2% 5-Bromo-3-(2-trimethylsilylacetylene)pyrazine-2-amine (1.22 g, 4.52 mmol)Dissolved in anhydrous DMF (10 mL), cooled to 0 C,Add sodium hydride (253 mg, 6.33 mmol, 60%),The resulting mixture was stirred at 0 C for 15 minutes and then p-toluenesulfonyl chloride ( 865 mg, 4.51 mmol).The resulting mixture was warmed to room temperature and the reaction was continued for 3 hours.It was quenched with ice water (40 mL) andEtOAc.The separated organic phase was washed with brine (60 mL).Dry over anhydrous sodium sulfate and concentrate the filtrate under reduced pressure.The residue obtained was purified by silica gel column chromatography(PE/EtOAc (nu/nu)=10/1),The title compound was obtained as a yellow solid (624mg, 39.2%).
30.7% The compound 2-amino-3-(trimethylsilylethynyl)-5-bromopyrazin 5a (5.0g, 18.5mmol) was dissolved in DMF (100ml), at 0 C added portionwise NaH (0.96g, 24 mmol), stirred for 2 hours, TsCl (4.6 g, 24 mmol) was added portionwise.After stirring at room temperature for 10 h, TLC showed the reaction was completed. 0 C about 100ml was added an aqueous solution of ammonium chloride, the aqueous phase was extracted three times with ethyl acetate (100 mL), the organic phases were combined,Once, dried over anhydrous sodium sulfate washed with brine, and dried to give the crude product under reduced pressure using a rotary evaporator,Through the column to give the title compound 5b (2.0g, 5.6mmol), a yield of 30.7%
2.16 g Step B: 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine to 2-bromo-5-tosyl-5H-pyrrolo[2,3-b]pyrazine [0184] To a solution of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (3.00 g, 11.1 mmol) in DMF (60 mL) at about 0 C. is added NaH (60% dispersion in mineral oil, 0.577 g, 14.4 mmol) in three portions. After about 15 min, p-toluenesulfonyl chloride (2.75 g, 14.4 mmol) is added and the reaction is allowed to warm slowly to ambient temperature. After about 16 h, the reaction mixture is poured onto ice-cold water (120 mL) and the precipitate is collected by vacuum filtration. The crude solid is dissolved in DCM (15 mL) and purified by silica gel chromatography eluting with DCM to give 2-bromo-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (2.16 g, 52%): LC/MS (Table 1, Method c) Rt=1.58 min; MS m/z: 352, 354 (M+H)+.

 

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Technical Information

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Related Functional Groups of
[ 875781-41-2 ]

Organosilicons

Chemical Structure| 86521-05-3

A103592 [86521-05-3]

2-((Trimethylsilyl)ethynyl)pyridine

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