Structure of 564443-27-2
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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.
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CAS No. : | 564443-27-2 |
Formula : | C7H3F3N2OS |
M.W : | 220.17 |
SMILES Code : | O=CC1=C(C(F)(F)F)N=C2SC=CN21 |
MDL No. : | MFCD05179682 |
InChI Key : | UZNYVYBQRNSEGZ-UHFFFAOYSA-N |
Pubchem ID : | 3760850 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 8 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 43.46 |
TPSA ? Topological Polar Surface Area: Calculated from |
62.61 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.58 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.38 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.82 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.78 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.24 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.12 |
Solubility | 0.167 mg/ml ; 0.000756 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.54 |
Solubility | 0.063 mg/ml ; 0.000286 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.2 |
Solubility | 1.4 mg/ml ; 0.00635 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) |
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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.81 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 |
1.0 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) |
2.41 |
* 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 |
---|---|---|
52% | With trichlorophosphate; In chloroform; at 0℃;Reflux; | The Vilsmeier reagent was prepared at 0-5 C. by dropping POCl3 0.262 mL (2.810 mmol) into a stirred solution of dry DMF 0.262 mL (3.383 mmol) in 0.4 mL of CHCl3. 6-trifluoromethyl-imidazo[2,1-b]thiazole (Moazzam M. et al, Indian Journal of Chemistry: Section B, 1988, 27B(11), 1051-1053) 100 mg (0.520 mmol) in 3 mL CHCl3 was added dropwise to the Vilsmeier reagent while maintening stirring and cooling. The reaction mixture was kept for 3 h at RT and under reflux for 39 h. After cooling to RT, the reaction mixture was poured into ice-water, extracted with DCM (3×), dried over MgSO4, filtered and concentrated under reduced pressure to give a crude oil.FC (n-heptane/EA:8/2 to 1/1) gave the title compound as an oil (360 mg, 52%).1H-NMR (CDCl3): delta=7.30 (d, 2H); 8.45 (s, 1H); 10.05 (s, 1H). |
With trichlorophosphate; In chloroform; at 0 - 20℃; for 63.0h;Heating / reflux; | At 00C POCl3 (17.1 mmol) is added dropwise to a solution of DMF (20.6 mmol) in chloroform (5.0 mL). A solution of 6-trifluoromethyl-imidazo[2,l-b]thiazole (3.17 mmol) in chloroform (15 mL) is added dropwise at 00C and the mixture is stirred for 3h at RT. After heating for 2.5d to reflux the mixture is poured into ice, extracted three times with DCM, dried over MgSO4 and concentrated under reduced pressure. DCM is added, the obtained precipitate is filtered off and the filtrate is concentrated in vacuo to give a crude product which is dissolved in tert.-butanol (19.5 mL). A solution of sodium chlorite (23.0 mmol) and NaH2PO4 (17.6 mmol) in water (19.5 mL) is added dropwise and the mixture is stirred for 90 min at RT. The solvents are partially removed in vacuo and the obtained precipitate is filtered off to give the desired product as a white solid. LC-MS: tR = 0.73 min; [M+H]+ = 237.2. | |
With trichlorophosphate; In chloroform; at 0 - 20℃; for 63.0h;Heating / reflux; | At 00C POCl3 (17.1 mmol) is added dropwise to a solution of DMF (20.6 mmol) in chloroform (5.0 mL). A solution of 6-trifluoromethyl-imidazo[2,l-b]thiazole (3.17 mmol) in chloroform (15 mL) is added dropwise at 00C and the mixture is stirred for 3h at RT. After heating for 2.5d to reflux the mixture is poured into ice, extracted three times with DCM, dried over MgSO4 and concentrated under reduced pressure. DCM is added, the obtained precipitate is filtered off and the filtrate is concentrated in vacuo to give a crude product which is dissolved in tert.-butanol (19.5 mL). A solution of sodium chlorite (23.0 mmol) and sodium dihydrogen phosphate dihydrate (17.6 mmol) in water (19.5 mL) is added dropwise and the mixture is stirred for 90 min at RT. The solvents are partially removed in vacuo and the obtained precipitate is filtered off to give the desired product as a white solid. LC-MS: tR = 0.73 min; [M+H]+ = 237.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With sodium chlorite; sodium dihydrogenphosphate dihydrate; In water; tert-butyl alcohol; at 20℃; | A solution of sodium chlorite 418.986 mg (4.633 mmol) and sodium dihydrogen phosphate dihydrate 553.971 mg (3.551 mmol) in water 3.94 mL (218.895 mmol) was added dropwise to a solution of <strong>[564443-27-2]6-trifluoromethyl-imidazo[2,1-b]thiazole-5-carbaldehyde</strong> 119 mg (0.54 mmol) in t-BuOH (3.94 mL). The mixture was stirred for 2 h30 at RT. The mixture was then concentrated in vacuo to remove t-BuOH, a white precipitate was formed and filtered to give the title compound as a white solid (70 mg, 55%).LC-MS: rt=0.74 min, 278 [M+H+MeCN]+. |
With sodium chlorite; sodium dihydrogenphosphate; In water; tert-butyl alcohol; at 20℃; for 1.5h;Heating / reflux; | At 00C POCl3 (17.1 mmol) is added dropwise to a solution of DMF (20.6 mmol) in chloroform (5.0 mL). A solution of 6-trifluoromethyl-imidazo[2,l-b]thiazole (3.17 mmol) in chloroform (15 mL) is added dropwise at 00C and the mixture is stirred for 3h at RT. After heating for 2.5d to reflux the mixture is poured into ice, extracted three times with DCM, dried over MgSO4 and concentrated under reduced pressure. DCM is added, the obtained precipitate is filtered off and the filtrate is concentrated in vacuo to give a crude product which is dissolved in tert.-butanol (19.5 mL). A solution of sodium chlorite (23.0 mmol) and NaH2PO4 (17.6 mmol) in water (19.5 mL) is added dropwise and the mixture is stirred for 90 min at RT. The solvents are partially removed in vacuo and the obtained precipitate is filtered off to give the desired product as a white solid. LC-MS: tR = 0.73 min; [M+H]+ = 237.2. | |
With sodium chlorite; sodium dihydrogenphosphate; water; In tert-butyl alcohol; at 20℃; for 1.5h; | At 00C POCl3 (17.1 mmol) is added dropwise to a solution of DMF (20.6 mmol) in chloroform (5.0 mL). A solution of 6-trifluoromethyl-imidazo[2,l-b]thiazole (3.17 mmol) in chloroform (15 mL) is added dropwise at 00C and the mixture is stirred for 3h at RT. After heating for 2.5d to reflux the mixture is poured into ice, extracted three times with DCM, dried over MgSO4 and concentrated under reduced pressure. DCM is added, the obtained precipitate is filtered off and the filtrate is concentrated in vacuo to give a crude product which is dissolved in tert.-butanol (19.5 mL). A solution of sodium chlorite (23.0 mmol) and sodium dihydrogen phosphate dihydrate (17.6 mmol) in water (19.5 mL) is added dropwise and the mixture is stirred for 90 min at RT. The solvents are partially removed in vacuo and the obtained precipitate is filtered off to give the desired product as a white solid. LC-MS: tR = 0.73 min; [M+H]+ = 237.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium hydroxide; In ethanol; water; at 27℃; for 4.0h; | Example 3(E)-3-(6-(trifluoromethyl) imidazo [2,1- b] tmazol-5-yl)-l-(3,4,5-trimethoxyphenyl) prop- 2-en-l-one (7f)To a stirred solution of trimethoxy acetophenone (210 mg, 1.0 mmol) and a 6- (trifluoromethyl) imidazo [2,1-b] thiazole-5-carbaldehyde (220 mg, 1.0 mmol) in ethanol (20ml) 10% aqueous solution of NaOH was added (5ml). The reaction mixture was stirred at room temperature 27C for 4 h and the reaction was monitored by TLC using ethyl acetate-hexane (3:7) as a solvent system. The solvent was evaporated under vacuum then the residue was dissolved in ethylacetate / water. The organic layer was washed with brine and evaporated. This was further purified by column chromatography using ethyl acetate: hexane (2:8) as a solvent system to obtain the pure product (7f) as yellow solid (329 mg, 80% yield). Mp: 177-180 C lH NMR (CDC13, 300 MHz), delta 3.94-3.96 (b, 9H), 7.17 (d, 1H, J = 15.86 Hz), 7.21 - 7.22 (b, 2H), 7.33 (d, 1H ,J= 5.86 Hz), 7.83 (d, 1H, J= 4.53 Hz ), 7.90 (d, 1H J= 15.86 Hz), ESI-MS:413.38 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium hydroxide; In ethanol; water; at 27℃; for 4.0h; | Example 5(E)-l-(3,4-dimethoxyphenyl)-3-(6-(trifluoromethyl) imidazo [2,1- b] thiazol-5-yl)Prop-2-en-l-one (8f)To a stirred solution 3,4-dimethoxyphenyl acetophenone (180 mg, 2.7 mmol) and a 6- (trifluoromethyl) imidazo [2,1-b] thiazole-5-carbaldehyde (246 mg, 2.7 mmol) in ethanol (20ml) 10% aqueous solution of NaOH was added (5ml). The reaction mixture was stirred at room temperature 27C for 4 h and the reaction was monitored by TLC using ethyl acetate-hexane (3:7) as a solvent system. The solvent was evaporated under vacuum then the residue was dissolved in ethylacetate / water. The organic layer was washed with brine and evaporated. This was further purified by columnchromatography using ethyl acetate: hexane (2:8) as a solvent system to obtain the pure product (8f) as yellow solid (306 mg, 75% yield). Mp: 167-169 C'H NMR (CDC13, 300 MHz), delta 3.97 (s, 6H), 6.93 (d, 1H, J= 9.065 Hz), 7.19 (d, 1H, J = 4.53. Hz), 7.41 (d, 1H, J= 15.86 Hz ), 7.57 -7.61 (m, 2H), 7.83 (d, 1H, J= 4.53 Hz), 7.91 (d, 1H J= 15.86 Hz) , ESI-MS:382.35 (M+H)+. |
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