Structure of 3,4-Diaminobenzotrifluoride
CAS No.: 368-71-8
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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.
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CAS No. : | 368-71-8 |
Formula : | C7H7F3N2 |
M.W : | 176.14 |
SMILES Code : | NC1=CC=C(C(F)(F)F)C=C1N |
MDL No. : | MFCD00042456 |
InChI Key : | RQWJHUJJBYMJMN-UHFFFAOYSA-N |
Pubchem ID : | 520822 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338-P309-P310 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 40.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.04 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.24 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.15 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.04 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.91 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.41 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.75 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.96 |
Solubility | 1.93 mg/ml ; 0.011 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.84 |
Solubility | 2.56 mg/ml ; 0.0145 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.56 |
Solubility | 0.482 mg/ml ; 0.00274 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 |
-6.56 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) |
1.14 |
* 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 |
---|---|---|
652 mg | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 4h;Inert atmosphere; | Step A: N-(2-amino-5-(trifluoromethyl)phenyn-4-chloro-2,5-difluorobenzamide A suspension of <strong>[132794-07-1]4-chloro-2,5-difluorobenzoic acid</strong> (1.00 g, 5.19 mmol), 3,4- diaminobenzotrifluoride (1.006 g, 5.71 mmol) and PyBOP (2.97 g, 5.71 mmol) in DMF (15.0 ml) under a N2 atmosphere was stirred at room temperature for 5 min. DIEA (2.72 ml, 15.58 mmol) was then added via a syringe and the mixture stirred at roomtemperature for 4 h. The mixture was diluted with water and extracted with EtOAc. The organic layer was dried (MgS04) and concentrated. Purification on the CombiFlash Companion, on a 40 g column eluting with 10 to 30 % EtOAc / Hexane afforded 652 mg of N-(2-amino-5-(trifluoromethyl)phenyl)-4-chloro-2,5-difluorobenzamide as a cream crystalline solid. LC- S (M+l) = 351. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In water; at 100 - 120℃; for 5.0h; | 12 M HCI (1 ml, 12 mmol) was added to a mixture of 4-(trifluoromethyl)benzene-1 ,2-diamine (1 g, 5.68 mmol) and chloroacetic acid (0.590 g, 6.25 mmol) in water (20 ml) and the mixture was heated at 100C for 2 h. Further 12 M HCI (4 ml, 48 mmol) was added and the reaction mixture heated at 120C for 3 h. The mixture was then cooled to room temperature and quenched by addition of 7 M ammonia in MeOH until basic, extracted with EtOAc (3 x 20 ml) and the combined organic layers were washed with brine (20 ml), dried (MgSC), filtered and evaporated in vacuo. Flash column chromatography (eluting with a gradient 5- 50% EtOAc / heptane) afforded the crude title compound as a purple solid (0.571 g, 24%, 56% purity) which was used without further purification. HPLCMS (Method E): [m/z]: 234.85 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 60℃; for 16h; | General procedure: The title compounds were prepared in parallel format using thefollowing protocol: Step 1: To 4-alkyl-1, 2-diaminobenzene (100 mumol,1 eq) was added a solution of the required amino acid in DMF (0.2 M,500 muL, 100 mumol, 1 eq) followed by TEA (28 muL, 200 mumol, 2 eq) and asolution of HATU in DMF (0.2 M, 500 muL, 100 mumol, 1 eq). The reactionwas shaken at 60 °C for 16 h before cooling and concentrating in vacuoto afford crude uncyclised intermediate. Step 2: To crude uncyclizedintermediate was added acetic acid (1000 muL) and the reaction wasshaken at 80 °C for 1 h. The reaction was cooled, concentrated in vacuoand dissolved in DMSO. The solution was filtered and purified usingpreparative HPLC to afford the intermediate benzimidazole. Step 3: Tothe intermediate benzimidazole was added CH2Cl2 (1800 mumol) followedby 4M HCI in dioxane (200 muL) and the reaction was shaken at30 °C for 1.5 h. The reaction was concentrated in vacuo to afford productas the HCl salt. |
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