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Structure of 564443-27-2

Chemical Structure| 564443-27-2

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Product Details of [ 564443-27-2 ]

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

Safety of [ 564443-27-2 ]

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

Computational Chemistry of [ 564443-27-2 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

62.61 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.63
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

2.58
Log Po/w (WLOGP)?

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

3.38
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.

0.82
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

2.78
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.24

Water Solubility

Log S (ESOL):?

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

-3.12
Solubility 0.167 mg/ml ; 0.000756 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.

-3.54
Solubility 0.063 mg/ml ; 0.000286 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

-2.2
Solubility 1.4 mg/ml ; 0.00635 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.

-5.81 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

1.0 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)

2.41

Application In Synthesis of [ 564443-27-2 ]

* 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 [ 564443-27-2 ]

[ 564443-27-2 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 109113-98-6 ]
  • [ 68-12-2 ]
  • [ 564443-27-2 ]
YieldReaction ConditionsOperation 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.
  • 2
  • [ 564443-27-2 ]
  • [ 1007874-87-4 ]
YieldReaction ConditionsOperation 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.
  • 4
  • [ 1136-86-3 ]
  • [ 564443-27-2 ]
  • (E)-3-(6-(trifluoromethyl)imidazo[2,1-b]thiazol-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation 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)+.
  • 5
  • [ 564443-27-2 ]
  • [ 1131-62-0 ]
  • [ 1257653-76-1 ]
YieldReaction ConditionsOperation 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)+.
  • 6
  • [ 1136-86-3 ]
  • [ 564443-27-2 ]
  • [ 1257653-74-9 ]
  • 7
  • BrH*C6H5F3N2OS [ No CAS ]
  • [ 564443-27-2 ]
  • 8
  • [ 564443-27-2 ]
  • [ 141-97-9 ]
  • [ 1308398-16-4 ]
 

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