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Chemical Structure| 54390-97-5 Chemical Structure| 54390-97-5

Structure of 54390-97-5

Chemical Structure| 54390-97-5

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Product Details of [ 54390-97-5 ]

CAS No. :54390-97-5
Formula : C3H2BrNS
M.W : 164.02
SMILES Code : BrC1=CC=NS1
MDL No. :MFCD11110322
InChI Key :XNONRNKAYRHZDJ-UHFFFAOYSA-N
Pubchem ID :12631174

Safety of [ 54390-97-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P210-P261-P280-P303+P361+P353-P305+P351+P338-P370+P378-P403+P235-P405-P501
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 54390-97-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 29.81
TPSA ?

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

41.13 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.5
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

2.01
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.

0.53
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

3.07
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.8

Water Solubility

Log S (ESOL):?

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

-2.74
Solubility 0.299 mg/ml ; 0.00182 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.

-2.5
Solubility 0.518 mg/ml ; 0.00316 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

-2.14
Solubility 1.2 mg/ml ; 0.00729 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.

-5.87 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)

2.6

Application In Synthesis of [ 54390-97-5 ]

* 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 [ 54390-97-5 ]

[ 54390-97-5 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 288-16-4 ]
  • [ 54390-97-5 ]
YieldReaction ConditionsOperation in experiment
21% To a solution of <strong>[288-16-4]isothiazol</strong>e (5 g, 0.06 mol) in anhydrous THF (50 mL) was added n- BuLi (28.2 mL, 0.07 mol) dropwise at -70 oC over 1 h. After stirring at -70 oC for 1 h, Br2 (6 mL, 0.12 mol) was added dropwise over 30 min and the resulting mixture was allowed to warm to RT and poured into an excess of cold 2N HCl solution. The organic layer was separated and the aqueous layer was extracted with Et2O (200 mL x 3). The combined organic extracts were washed with saturated sodium dithionite solution (200 mL x 2), dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated in vacuo, and the resulting residue was distilled to afford 5-bromo<strong>[288-16-4]isothiazol</strong>e (2 g, 21%) as yellow oil.1H NMR (400 MHz, CDCl3) delta 8.33 (d, J = 1.6 Hz, 1H), 7.28 (d, J = 1.6 Hz, 1H).
Under nitrogen protection, compound 1 was added(20 g, 0.235 mol) was added to dry 100 ml of ether and stirred to dissolve,And then cooled to below 0 ,To this was added n-butyllithium (0.24 mol)During the dropping process, the temperature was kept below 0 C,After the dropwise addition, the incubation reaction was carried out until no compound 1 was added.To the reaction solution was added bromine (0.5 mol)During the dropping process, the temperature was kept below 0 C,After completion of the dropwise addition, the temperature was gradually raised to room temperature, and after stirring for half an hour, the reaction was quenched by adding thereto a hydrochloric acid solution (2N, 500 ml). (100ml * 2), dried over anhydrous sodium sulfate, filtered and concentrated to dryness. After drying, the aqueous phase was washed with diethyl ether (200ml * 3) and extracted.To give the yellow oily compound 2.
Compound 1 (20 g, 0.235 mol) was added under stirring with nitrogen to dry 100 ml of ether and stirred and dissolvedThe temperature is 0 C or lower, n-butyllithium (0.24 mol) is added dropwise thereto, and the mixture is kept at 0 C or lower during the dropwise addition.Temperature reaction until no compound 1.To the reaction solution was added dropwise bromine (0.5 mol), and the mixture was kept below 0 C during the dropwise addition, and the mixture was gradually raised toAfter stirring for half an hour, the reaction was quenched by adding hydrochloric acid solution (2N, 500 ml) thereto.And the aqueous phase was extracted with ether (200 ml * 3) and discarded. The organic phase was combined and washed with sodium dithionite solution(100 ml * 2), dried over anhydrous sodium sulfate, filtered and concentrated to dryness to give compound 2 as a yellow oil.
Under nitrogen, compound l (20 g, 0.235 mol)Add 100 ml of dry ether to dry,Then cool down to below 0 C,To this was added n-butyllithium (0.24mo 1)During the dropping process, it is kept below 0 C,After the dropwise addition, the incubation reaction was carried out until no compound 1 was added.To the reaction solution was added bromine (0.5 mol)During the dropping process, it is kept below 0 C,After the dropwise addition, slowly raise to room temperature,After stirring for half an hour, the reaction was quenched by the addition of hydrochloric acid solution (2N, 500 ml).And the aqueous phase was extracted with ether (200 ml * 3) and discarded. The organic phase was combined and washed with sodium dithionite solution(100 ml * 2), dried over anhydrous sodium sulfate, filtered and concentrated to dryness to give compound 2 as a yellow oil.
Compound 1 (20 g, 0.235 mol) was added under stirring with nitrogen to dry 100 ml of ether and stirred to dissolve,And then cooled to below 0 ,To this was added n-butyllithium (0.24 mol)During the dropping process, the temperature was kept below 0 C,After the dropwise addition, the incubation reaction was carried out until no compound 1 was added.To the reaction solution was added bromine (0.5 mol)During the dropping process, the temperature was kept below 0 C,After the dropwise addition, slowly raise to room temperature,After stirring for half an hour, the reaction was quenched by the addition of hydrochloric acid solution (2N, 500 ml).The aqueous phase was extracted with ether (200 ml * 3) and discarded.The combined organic phase, sodium dithionite solution (100 ml * 2)Dried over anhydrous sodium sulfate, filtered and concentrated to dryness,A yellow oily compound was prepared.
Compound l (20 g, 0.235 mol) was added under stirring with nitrogen to dry 100 ml of ether and stirred to dissolve,Then cooled to below 0 C, to which n-butyllithium (0.24mo 1) was added dropwise,During the dropwise addition, the reaction was kept below 0 C and the incubation was completed until the compound 1 was added.To the reaction solution was added bromine (0.5 mol)Dropping the process to maintain the following 0 C, drop out after the completion of slowly rose to room temperature,After stirring for half an hour, the reaction was quenched by the addition of hydrochloric acid solution (2N, 500 ml).And the aqueous phase was extracted with ether (200 ml * 3) and discarded. The organic phase was combined and washed with sodium dithionite solution(100 ml * 2), dried over anhydrous sodium sulfate, filtered and concentrated to dryness to give compound 2 as a yellow oil.[0188] In this step, the ether can also be replaced with a solvent such as methyl ether, dimethyl ether, tetrahydrofuran, 1,4-dioxane and the like.
With n-butyllithium; bromine; In diethyl ether; at 0 - 20℃; for 0.5h;Inert atmosphere; Compound 1 (20 g, 0.235 mol 1) was added to dry 100 ml of diethyl ether under stirring under nitrogen and then cooled to below 0 C, n-butyllithium (0.24 mol 1) was added dropwise thereto, 0 C or less, dropwise after completion of the incubation until no compound 1 is added.To the reaction solution was added dropwise bromine (0.5 mol), and the mixture was kept below 0 C during the dropwise addition. After the completion of the dropwise addition, the temperature was gradually raised to room temperature. After stirring for half an hour, the hydrochloric acid solution (2N, 500 ml) TheAnd the aqueous phase was extracted with ether (200 ml * 3) and discarded. The organic phase was combined and washed with sodium dithionite solution(100 ml * 2), dried over anhydrous sodium sulfate, filtered and concentrated to dryness to give compound 2 as a yellow oil.In this step, the ether can also be replaced with a solvent such as methyl ether, dimethyl ether, tetrahydrofuran, 1,4-dioxane and the like.
Under nitrogen protection, compound 1 was added(20 g, 0.235 mol) was added to dry 100 ml of ether and stirred and dissolvedTemperature below 0 ,To this was added n-butyllithium (0.24 mol), and the mixture was kept at 0 C or less during the dropping,After the dropwise addition, the incubation reaction was carried out until no compound 1 was added.To the reaction solution was added bromine (0.5 mol)The reaction mixture was kept at 0 C or lower, and the mixture was slowly added to the room temperature after completion of the dropwise addition. After stirring for half an hour, the reaction was quenched by adding hydrochloric acid solution (2N, 500 ml) thereto.And the aqueous phase was extracted with ether (200 ml * 3) and discarded. The organic phase was combined and washed with sodium dithionite solution(100 ml * 2), dried over anhydrous sodium sulfate, filtered and concentrated to dryness to give compound 2 as a yellow oil.
Compound 1 (20 g, 0.235 mol) was added under stirring with nitrogen to dry 100 ml of ether and stirred to dissolve,And then cooled to below 0 ,To this was added n-butyllithium (0.24 mol)During the dropping process, the temperature was kept below 0 C,After the dropwise addition, the incubation reaction was carried out until no compound 1 was added.To the reaction solution was added bromine (0.5 mol)During the dropping process, the temperature was kept below 0 C,After the dropwise addition, slowly raise to room temperature,After stirring for half an hour, the reaction was quenched by the addition of hydrochloric acid solution (2N, 500 ml).The aqueous phase was extracted with ether (200 ml * 3) and discarded.The combined organic phase, sodium dithionite solution (100 ml * 2)Dried over anhydrous sodium sulfate, filtered and concentrated to dryness,A yellow oily compound was prepared.
Compound 1 (20 g, 0.235 mol) was added under stirring with nitrogen to dry 100 ml of ether and stirred to dissolve,And then cooled to 0 C or lower, to which n-butyllithium (0.24 mol)During the dropwise addition, the temperature was kept below 0 C, and the reaction was carried out until the compound 1 was added.To the reaction solution was added bromine (0.5 mol), and the mixture was kept at 0 C or less during the dropping,After completion of the dropwise addition, the temperature was gradually raised to room temperature, and after stirring for half an hour, the hydrochloric acid solution (2N, 500 ml)Quenching reaction.The aqueous phase was extracted with ether (200 ml * 3) and discarded. The organic phases were combined,Sodium dithionite solution (100ml * 2), dried over anhydrous sodium sulfate, filtered and concentrated to dryness,A yellow oily compound was prepared.In this step, the ether can also be replaced with a solvent such as methyl ether, dimethyl ether, tetrahydrofuran, 1,4-dioxane and the like.
With n-butyllithium; bromine; In diethyl ether; at 0 - 20℃; for 0.5h;Inert atmosphere; Under a nitrogen atmosphere, compound 1 (20 g, 0.235 mol)Add 100 ml of dry ether to dry,And then cooled to below 0 ,To this was added n-butyllithium (0.24 mol)During the dropping process, the temperature was kept below 0 C,After the dropwise addition, the incubation reaction was carried out until no compound 1 was added.To the reaction solution was added bromine (0.5 mol)During the dropping process, the temperature was kept below 0 C,After the dropwise addition, slowly raise to room temperature,After stirring for half an hour, the reaction was quenched by the addition of hydrochloric acid solution (2N, 500 ml).Layered,The aqueous phase was extracted with ether (200 ml * 3) and discarded.Combined organic phase,Sodium dithionite solution(100 ml * 2),Dried over anhydrous sodium sulfate,Filtered and concentrated to dry,A yellow oily compound was prepared.In this step, the ether can also be treated with methyl ether, dimethyl ether, tetrahydrofuran,1,4-dioxane and other solvents instead.
With n-butyllithium; bromine; In diethyl ether; at 0 - 20℃; for 0.5h;Inert atmosphere; Compound 1 (20 g, 0.235 mol) was added to dry 100 ml of diethyl ether under nitrogen atmosphere and stirred to dissolve,And then cooled to 0 C or lower, n-butyllithium (0.24 mol) was added dropwise thereto, and the temperature was kept below 0 C during the dropwise addition, and the reaction was carried out until the compound 1 was added.To the reaction solution was added bromine (0.5 mol), and the mixture was kept at 0 C or less during the dropping,After completion of the dropwise addition, the temperature was gradually raised to room temperature, and after stirring for half an hour, the hydrochloric acid solution was added thereto(2N, 500 ml).And the aqueous phase was extracted with ether (200 ml * 3) and discarded. The combined organic phase and sodium dithionite solution were washed(100 ml * 2), dried over anhydrous sodium sulfate, filtered and concentrated to dryness to give compound 2 as a yellow oil.In this step, the ether can also be replaced with a solvent such as methyl ether, dimethyl ether, tetrahydrofuran, 1,4-dioxane and the like.
With n-butyllithium; bromine; In diethyl ether; at 0 - 20℃; for 0.5h;Inert atmosphere; Under nitrogen, compound l (20 g, 0.235 mol) was added to dry 100 ml of ether and stirred and dissolved(0.24 mol 1) was added dropwise thereto at a temperature below 0 C, and the mixture was kept at 0 C or less during the dropwise addition.Temperature reaction until no compound 1.To the reaction solution was added dropwise bromine (0.5 mol)During the dropping process, it is kept below 0 C,After the dropwise addition, slowly rise to room temperature,After stirring for half an hour, the reaction was quenched by the addition of hydrochloric acid solution (2N, 500 ml).Layered,The aqueous phase was treated with ether (200 ml * 3)After extraction,Combined organic phase,Sodium dithionite solution (100 ml * 2),Dried over anhydrous sodium sulfate,Filtered and concentrated to dry,To give a yellow oily compound.

 

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