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Structure of 54390-97-5
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
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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 |
GHS Pictogram: |
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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: | Ⅲ |
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 |
41.13 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.5 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.01 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.53 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.07 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.8 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.74 |
Solubility | 0.299 mg/ml ; 0.00182 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.5 |
Solubility | 0.518 mg/ml ; 0.00316 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.14 |
Solubility | 1.2 mg/ml ; 0.00729 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.87 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.6 |
* 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.
Yield | Reaction Conditions | Operation 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. |