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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Structure of 395-44-8
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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. : | 395-44-8 |
Formula : | C8H6BrF3 |
M.W : | 239.03 |
SMILES Code : | FC(C1=CC=CC=C1CBr)(F)F |
MDL No. : | MFCD00013558 |
InChI Key : | TXVVVEUSVBLDED-UHFFFAOYSA-N |
Pubchem ID : | 123057 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H314-H290 |
Precautionary Statements: | P501-P234-P264-P280-P390-P303+P361+P353-P301+P330+P331-P363-P304+P340+P310-P305+P351+P338+P310-P406-P405 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.49 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.36 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.6 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.83 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.68 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.68 |
Solubility | 0.0503 mg/ml ; 0.00021 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.04 |
Solubility | 0.219 mg/ml ; 0.000916 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.55 |
Solubility | 0.00678 mg/ml ; 0.0000284 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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) |
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) |
Yes |
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 |
-5.37 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 |
1.0 |
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) |
1.79 |
* 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 |
---|---|---|
55% | With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0℃; for 1h;Inert atmosphere; | Synthesis of2-chloro-8-(2-(trifluoromethyl) benzyl)-7, 8-dihydro-6H-pyrimido [5, 4-b] [I, 4] oxazine [0458] To a stirred solution of 2-chloro-7, 8-dihydro-6H-pyrimido [5, 4-b] [1, 4] oxazine (150 mg, 0.87 mmol) in DMF (3 mL) under argon atmosphere were added sodium hydride (42 mg, 1.75 mmol) portion- wise for 5 min then l-(bromomethyl)-2-(trifluoromethyl) benzene (251 mg, 1.05 mmol) at 0 C. The reaction mixture was stirred for 1 h at 0 C. After consumption of the starting materials (monitored by TLC), the reaction was diluted with cold water (50 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was washed with n-pentane (2 x 5 mL) to afford 2-chloro-8-(2-(trifluoromethyl) benzyl)-7, 8-dihydro-6H- pyrimido [5, 4-b] [1, 4] oxazine (160 mg, 55%) as an off-white solid. 1H-NMR (DMSO-<, 400 MHz): delta 7.79-7.77 (m, 2H), 7.65 (t, 1H), 7.52 (t, 1H), 7.40 (d, 1H), 4.95 (s, 2H), 4.29- 4.23 (m, 2H), 3.57-3.50 (m, 2H); LCMS: 329.8 (M+l); (column; X-Select CSH C-18 (50 3.0 mm, 3.5 mupiiota); RT 3.87 min. 0.05% Aq TFA: ACN; 0.80 mL/min); UPLC (purity): 92.4%; (column; Acquity UPLC BEH C-18 2.1 X 50 mm, 1.7 mupiiota); RT 2.57 min. ACN: 0.025% TFA (Aq); 0.50 mL/min; TLC: 30% EtOAc:hexanes (R 0.6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
148 mg | With potassium carbonate; In acetone; at 20℃; for 5h; | To a solution of <strong>[939-69-5]2-cyano-6-hydroxybenzothiazole</strong> (100 mg, 0.568 mmol) in 10 mL of acetone was added potassiumcarbonate (157 mg, 1.14 mmol), followed by 2-(trifluoromethyl)benzyl bromide (204 mg, 0.852 mmol). Themixture was then stirred at RT for about 5 hrs. The solvent was then removed under reduced pressure and the residuewas dissolved in dichloromethane. The resultant solution was then extracted with dichloromethane. The organic phasewas dried over sodium sulfate and purified by flash chromatography using dichloromethane. 148 mg of product wasobtained.1H NMR (CDCl3):8.12 ppm (d, 1H), 7.75 ppm (d, 2H), 7.60 ppm (t, 1H), 7.48 ppm (t, 1H), 7.41 ppm (d, 1H),7.34 ppm (dd, 1H), 5.28 ppm (s, 2H) 19F NMR (CDC13): 61 ppmMS: ES+: 335.74 (M.W. 334.32) |
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 |
---|---|---|
85.3% | General procedure: The mixture of stirred DTET (100 mg, 0.16 mmol) and NaH (20 mg,0.83 mmol) was dissolved in 2 mL DMF at 0 C. Then, R1Br (0.18 mmol)dissolved in 0.5 mL DMF was added to the DTET solution, and themixture was stirred until the TLC analysis showed that the reaction wascompleted. The temperature of the mixture was cooled to room temperatureand vacuum evaporated. The residue was purified using aluminumcolumn chromatography, and 3a-3m were obtained usingCH2Cl2/CH3OH as the eluent | |
5.25 g | With triethylamine; In ethyl acetate; at -10℃; for 72h; | Weigh 6.10g of <strong>[436-77-1]fangchinoline</strong> dissolved in 200mL of ethyl acetate in a 500mL three-necked flask.Add triethylamine10mL, 2.90g of o-trifluoromethylbenzyl bromide, stirred, cooled to -10 C and incubated for 72 h, TLC detection of <strong>[436-77-1]fangchinoline</strong> The reaction was carried out, warmed to room temperature, extracted with ethyl acetate three times (200 mL×3), evaporated under reduced pressure to a liquid volume of 60 mL, cooled to 5 C overnight, filtered, TLC followed by separation and purification of the product, solids Drying at 60 C for 4 h gave 5.25 g of product as a pale yellow powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: The mixture of stirred DTET (100 mg, 0.16 mmol) and NaH (20 mg,0.83 mmol) was dissolved in 2 mL DMF at 0 C. Then, R1Br (0.5 mmol)dissolved in 0.5 mL DMF was added to the DTET solution, and themixture was stirred at 0 C for 6 h, then heated to 92 C until the TLCanalysis showed that the reaction was completed. The temperature ofthe mixture was cooled to room temperature and vacuum evaporated.The residue was purified using aluminum column chromatography, and4a-4 h were obtained using CH2Cl 2/CH3OH as the eluent. |
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