Structure of 185613-91-6
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CAS No. : | 185613-91-6 |
Formula : | C10H8N2O2S |
M.W : | 220.25 |
SMILES Code : | NC1=NC(C2=CC=C(OCO3)C3=C2)=CS1 |
MDL No. : | MFCD01366560 |
InChI Key : | AKVSKDDSOWLASE-UHFFFAOYSA-N |
Pubchem ID : | 727580 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 11 |
Fraction Csp3 | 0.1 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 58.02 |
TPSA ? Topological Polar Surface Area: Calculated from |
85.61 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.05 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.08 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.84 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.87 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.99 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.99 |
Solubility | 0.224 mg/ml ; 0.00102 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.51 |
Solubility | 0.0685 mg/ml ; 0.000311 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.21 |
Solubility | 0.135 mg/ml ; 0.000612 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 |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.17 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 |
0.0 |
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) |
2.45 |
* 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 |
---|---|---|
Example 2 2-(4-Benzo-5-yl-thiazol-2-ylcarbamoyl)-pyrrolidine-1-carboxylic acid benzyl ester (Compound 5002) Using General Procedure G from 10 mg of4-Benzo[1,2]dioxol-5-yl-thiazol-2-ylamine in 1 mL of solution. MS: 452.0 (M+H+). General Procedure G A mixture of Z-Pro-OH (0.96 g, 3.84 mmol), HATU (1.46 g, 3.84 mmol), and DIEA (0.094 mL, 5.4 mmol) in DMF (30 mL) was stirred at room temperature for 1 hour. 1 or 2 mL of this solution was added to the amines described in the following Examples and reaction mixtures stirred at room temperature overnight. The resulting mixtures were diluted with DMF (5 mL) and water (0.5 mL) and purified using reverse phase HPLC to furnish the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | In pyridine; | EXAMPLE 16 2-[4-(benzo[1,3]dioxol-5-yl)-thiazol-2-ylaminocarbonyl]-benzoic acid Prepared analogously to Example 1d from <strong>[185613-91-6]2-amino-4-benzo[1,3]dioxol-5-yl-thiazole</strong> and phthalic anhydride in pyridine. Yield: 71% of theory, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With iodine; copper(II) oxide; In ethanol; at 78℃; | General procedure: A mixture of acetophenone 1a (120 mg, 1 mmol), iodine (279.2 mg, 1.1 mmol), and CuO (88 mg, 1.1 mmol) in anhydrous ethanol (30 mL) was heated at reflux, after disappearance of the reactant (1-12 h, monitored by TLC), thiourea 2 (76 mg, 1 mmol) was added and the mixture was refluxed for 1 h. After that, the solvent was removed under reduce pressure, and added 50 mL water to the residue, then extracted with EtOAc three times (3×50 mL). The extract was washed with 10% Na2S2O3 then a small amount 5% NaOH solution, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel using petroleum ether/EtOAc as the eluent to give the expected products 3a in 90% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21.2% | (Benzo [d] [1,3] dioxol-5-yl) thiazol-2-amine (2)(1.00 g, 4.54 mmol) and NaH (0.164 g, 6.82 mmol) were dissolved in THF (15 ml) and reacted at room temperature for 1 hour under a nitrogen stream. Benzyl bromide (1.17 g, 6.82 mmol) was then slowly added dropwise at room temperature and allowed to react for 10 minutes. After the reaction was completed, the reaction mixture was concentrated under reduced pressure, dissolved in ethyl acetate, and saturated NaHCO 3 solution was added thereto. The ethyl acetate layer was separated, dried over anhydrous Na2SO4 and then purified by column chromatography (Ethyl acetate: Hexane = 1: 5) to obtain Compound 1a. Yield: 21.2% | |
21% | General procedure: A solution of <strong>[185613-91-6]4-(benzo[d][1,3]dioxol-5-yl)thiazol-2-amine</strong> (1.0 equiv) and NaH (1.5 equiv) in THF was stirred at room temperature. After 1 h, benzyl bromide (1.5 equiv) was added and stirring was continued for 10 more min. The reaction progress was monitored by TLC. After completion of the reaction, quenched with saturated NH4Cl solution and extracted with EtOAc, the organic layer was dried over MgSO4, filtered, concentrated invacuo. The residue was purified by silica gel column chromatography (16% EtOAc/hexanes) to afford desired product. 4-(Benzo[d][1,3]dioxol-5-yl)-N-benzylthiazol-2-amine (7a)Yield 21%IR (neat) 3204, 1548, 864 cm-1;1H NMR (CDCl3, 400 MHz)delta7.30 (m, 7H), 6.76 (d, 1H,J= 8.1 Hz,), 6.51 (s, 1H), 5.93 (s, 2H), 4.45 (s, 2H);13C NMR (CDCl3, 100 MHz)delta169.4, 150.9, 147.8, 147.2, 137.7, 129.4, 128.9, 128.6, 127.7, 119.3, 108.4, 106.7, 101.1, 99.7, 49.8; HRMSm/z[M+H]+calculated for C17H15N2O2S: 311.0854; found 311.0872. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | General procedure: A solution of <strong>[185613-91-6]4-(benzo[d][1,3]dioxol-5-yl)thiazol-2-amine</strong> (1.0 equiv) and NaH (1.5 equiv) in THF was stirred at room temperature. After 1 h, benzyl bromide (1.5 equiv) was added and stirring was continued for 10 more min. The reaction progress was monitored by TLC. After completion of the reaction, quenched with saturated NH4Cl solution and extracted with EtOAc, the organic layer was dried over MgSO4, filtered, concentrated invacuo. The residue was purified by silica gel column chromatography (16% EtOAc/hexanes) to afford desired product. | |
16.9% | <strong>[185613-91-6]4-(benzo[d][1,3]dioxo-5-yl)thiazol-2-amine</strong>(2) (1.00 g, 4.54 mmol) and NaH (0.164 g, 6.82 mmol) to THF (15 ml) todissolved and then allowed to react at room temperature for 1 hour under a nitrogen stream. Then slowly added dropwise at room temperature, 2-(trifluoromethyl) benzyl bromide (1.63 g, 6.82 mmol) and allowed to react for 10 minutes. After thereaction was finished, it was concentrated under reduced pressure and extracted three times into a saturated solution of NaHCO3 is dissolved in ethyl acetate. The ethyl acetate layer was separated and dried with anhydrous Na2SO4, then purified by column chromatography (Ethyl acetate: Hexane = 1: 5) to give the compound 1b to give. Yield 16.9%, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17.2% | 4-(Benzo[d] [1,3]dioxol-5-yl)thiazol-2-amine(2) (1.00 g, 4.54 mmol) and NaH (0.164 g, 6.82 mmol) to THF (15 ml) todissolved and then allowed to react at room temperature for 1 hour under a nitrogen stream. Then slowly added dropwise atroom temperature 3a(trifluoromethyl) benzyl bromide (1.63 g, 6.82 mmol) and allowed to react for 10 minutes. After thereaction was finished, it was concentrated under reduced pressure and extracted three times into a saturated solution ofNaHCO3 is dissolved in ethyl acetate. The ethyl acetate layer was separated and dried with anhydrous Na2SO4, then purifiedby column chromatography (Ethyl acetate: Hexane = 1: 5) to give the compound 1c to give. Yield 17.2% | |
17% | General procedure: A solution of <strong>[185613-91-6]4-(benzo[d][1,3]dioxol-5-yl)thiazol-2-amine</strong> (1.0 equiv) and NaH (1.5 equiv) in THF was stirred at room temperature. After 1 h, benzyl bromide (1.5 equiv) was added and stirring was continued for 10 more min. The reaction progress was monitored by TLC. After completion of the reaction, quenched with saturated NH4Cl solution and extracted with EtOAc, the organic layer was dried over MgSO4, filtered, concentrated invacuo. The residue was purified by silica gel column chromatography (16% EtOAc/hexanes) to afford desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | General procedure: A solution of <strong>[185613-91-6]4-(benzo[d][1,3]dioxol-5-yl)thiazol-2-amine</strong> (1.0 equiv) and NaH (1.5 equiv) in THF was stirred at room temperature. After 1 h, benzyl bromide (1.5 equiv) was added and stirring was continued for 10 more min. The reaction progress was monitored by TLC. After completion of the reaction, quenched with saturated NH4Cl solution and extracted with EtOAc, the organic layer was dried over MgSO4, filtered, concentrated invacuo. The residue was purified by silica gel column chromatography (16% EtOAc/hexanes) to afford desired product. | |
16.7% | 4-(Benzo[d] [1,3]dioxol-5-yl)thiazol-2-amine(2) (1.00 g, 4.54 mmol) and NaH (0.164 g, 6.82 mmol) to THF (15 ml) todissolved and then allowed to react at room temperature for 1 hour under a nitrogen stream. Then slowly added dropwise atroom temperature to 4-(trifluoromethyl) benzyl bromide (1.63g, 6.82mmol) and the reaction was carried out for 10 minutes.After the reaction was finished, it was concentrated under reduced pressure and extracted three times into a saturatedsolution of NaHCO3 is dissolved in ethyl acetate. The ethyl acetate layer was separated and dried with anhydrous Na2SO4,then purified by column chromatography (Ethyl acetate: Hexane = 1: 5) to give the compound 1d to give. Yield 16.7% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | General procedure: A solution of <strong>[185613-91-6]4-(benzo[d][1,3]dioxol-5-yl)thiazol-2-amine</strong> (1.0 equiv) and NaH (1.5 equiv) in THF was stirred at room temperature. After 1 h, benzyl bromide (1.5 equiv) was added and stirring was continued for 10 more min. The reaction progress was monitored by TLC. After completion of the reaction, quenched with saturated NH4Cl solution and extracted with EtOAc, the organic layer was dried over MgSO4, filtered, concentrated invacuo. The residue was purified by silica gel column chromatography (16% EtOAc/hexanes) to afford desired product. | |
17.6% | 4-(Benzo[d][1,3]dioxol-5-yl)thiazol-2-amine(2) (1.00 g, 4.54 mmol) and NaH (0.164 g, 6.82 mmol) to THF (15 ml) todissolved and then allowed to react at room temperature for 1 hour under a nitrogen stream. After dropwise addition of 2-chlorobenzylbromide (1.40 g, 6.82 mmol) slowly at room temperature and reacted for 10 minutes. After the reaction wasfinished, it was concentrated under reduced pressure and extracted three times into a saturated solution of NaHCO3 isdissolved in ethyl acetate. The ethyl acetate layer was separated and dried with anhydrous Na2SO4, then purified by columnchromatography (Ethyl acetate: Hexane = 1: 5) to give the compound 1e to give. Yield 17.6% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17.4% | 4-(Benzo[d][1,3] dioxol-5-yl)thiazol-2-amine(2) (1.00 g, 4.54 mmol) and NaH (0.164 g, 6.82 mmol) to THF (15 ml) todissolved and then allowed to react at room temperature for 1 hour under a nitrogen stream. After dropwise addition of 3-chlorobenzylbromide (1.40 g, 6.82 mmol) slowly at room temperature and reacted for 10 minutes. After the reaction wasfinished, it was concentrated under reduced pressure and extracted three times into a saturated solution of NaHCO3 isdissolved in ethyl acetate. The ethyl acetate layer was separated and dried with anhydrous Na2SO4, then purified by columnchromatography (Ethyl acetate: Hexane = 1: 5) to give the compound 1f to give. Yield 17.4% | |
17% | General procedure: A solution of <strong>[185613-91-6]4-(benzo[d][1,3]dioxol-5-yl)thiazol-2-amine</strong> (1.0 equiv) and NaH (1.5 equiv) in THF was stirred at room temperature. After 1 h, benzyl bromide (1.5 equiv) was added and stirring was continued for 10 more min. The reaction progress was monitored by TLC. After completion of the reaction, quenched with saturated NH4Cl solution and extracted with EtOAc, the organic layer was dried over MgSO4, filtered, concentrated invacuo. The residue was purified by silica gel column chromatography (16% EtOAc/hexanes) to afford desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17.1% | 4-(Benzo[d][1,3]dioxol-5-yl)thiazol-2-amine(2) (1.00 g, 4.54 mmol) and NaH (0.164 g, 6.82 mmol) to THF (15 ml) todissolved and then allowed to react at room temperature for 1 hour under a nitrogen stream. After dropwise addition of 4chlorobenzylbromide (1.40 g, 6.82 mmol) slowly at room temperature and reacted for 10 minutes. After the reaction wasfinished, it was concentrated under reduced pressure and extracted three times into a saturated solution of NaHCO3 isdissolved in ethyl acetate. The ethyl acetate layer was separated and dried with anhydrous Na2SO4, then purified by columnchromatography (Ethyl acetate: Hexane = 1: 5) to give the compound 1g to give. Yield 17.1% | |
17% | General procedure: A solution of <strong>[185613-91-6]4-(benzo[d][1,3]dioxol-5-yl)thiazol-2-amine</strong> (1.0 equiv) and NaH (1.5 equiv) in THF was stirred at room temperature. After 1 h, benzyl bromide (1.5 equiv) was added and stirring was continued for 10 more min. The reaction progress was monitored by TLC. After completion of the reaction, quenched with saturated NH4Cl solution and extracted with EtOAc, the organic layer was dried over MgSO4, filtered, concentrated invacuo. The residue was purified by silica gel column chromatography (16% EtOAc/hexanes) to afford desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41.3% | In ethanol; at 66 - 80℃; for 24h;Inert atmosphere; | Benzo [d] [1,3] dioxol-5-yl) -2-bromoethanone (3)(3.00 g, 12.3 mmol) was dissolved in ethanol (150 ml), and then thiourea (1.88 g, 24.7 mmol) was added thereto and reacted at 66-80 C for 24 hours under a nitrogen stream. After the reaction was completed, the reaction mixture was concentrated under reduced pressure, dissolved in ethyl acetate, and saturated NaHCO3 solution was added thereto. The ethyl acetate layer was separated, dried over anhydrous Na2SO4, and purified by column chromatography (THF: Hexane = 1: 3). Yield: 41.3%. |
41% | In ethanol; at 80℃; for 24h; | To a solution of 1-(benzo[d][1,3]dioxol-5-yl)-2-bromoethan-1-one (5) (1.0 equiv.) in EtOH was added thiourea (2.0 equiv.) and stirred at 80C for 24 h. The reaction progress was monitored by TLC and the solvent was removed invacuoand then added saturated NaHCO3solution, extracted with EtOAc, the organic layer was dried over MgSO4, filtered, concentrated invacuo. The residue was purified by silica gel column chromatography (25% THF/hexanes) to afford desired product (41%).1H NMR (MeOD, 400 MHz)delta7.26 (dd, 1H,J= 8.1, 1.7 Hz) 7.20 (d, 1H,J= 1.7 Hz), 6.79 (d, 1H,J= 8.1 Hz), 6.64 (s, 1H), 5.93 (s, 2H). |
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