Structure of Bicalutamide impurity D
CAS No.: 654-70-6
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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. : | 654-70-6 |
| Formula : | C8H5F3N2 |
| M.W : | 186.13 |
| SMILES Code : | C1=CC(=CC(=C1C#N)C(F)(F)F)N |
| MDL No. : | MFCD00042155 |
| InChI Key : | PMDYLCUKSLBUHO-UHFFFAOYSA-N |
| Pubchem ID : | 522170 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H317 |
| Precautionary Statements: | P261-P264-P270-P272-P280-P301+P312+P330-P302+P352-P333+P313-P362+P364-P501 |
| Num. heavy atoms | 13 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.12 |
| Num. rotatable bonds | 1 |
| Num. H-bond acceptors | 4.0 |
| Num. H-bond donors | 1.0 |
| Molar Refractivity | 40.56 |
| TPSA ? Topological Polar Surface Area: Calculated from |
49.81 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.32 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.84 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.32 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.86 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.11 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.09 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-2.43 |
| Solubility | 0.694 mg/ml ; 0.00373 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.51 |
| Solubility | 0.58 mg/ml ; 0.00311 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.01 |
| Solubility | 0.181 mg/ml ; 0.000973 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 |
-6.13 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) |
1.69 |
* 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 |
|---|---|---|
| With triethylamine; In dichloromethane; | 2-ethoxy-6-pentadecyl-benzoyl chloride was condensed with 4-Amino-2-trifluromethyl benzonitrile in dichloromethane in presence of triethylamine as acid scavenger to yield N-(4-Cyano-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide. The reaction mixture was then concentrated in vacuo and the residue was extracted into ethyl acetate. The ethyl acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product. 1H-NMR:delta6.95-8.01 (7H,aromatic), delta3.98(2H,m,OCH2), delta1.33(3H,t,Methyl) |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1.3 g | With sodium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 5h; | 0.30g (0.0075 mol) of sodium hydroxide was added to a solution of 0.7g(0.0037 mol) of 4-amino-2-(trifluoromethyl)benzonitrile in 40 mL of DMF, followed by addition of 1g (0.0037 mol) of <strong>[1897-41-2]2,3,5,6-<strong>[1897-41-2]tetrachloroterephthalonitrile</strong></strong> understirring, the mixture was stirred for 5 h after addition at room temperature. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into water, solid precipitated and filtered under reducedpressure to give 1.3 g of compound C-38 as yellow solid, m.p. 176-178°C.[0117] 1H-NMR (300MHz, internal standard TMS, solvent CDCl3) delta(ppm): 6.86(dd, 1H, Ph-6-1H),7.16 (d, 1H, Ph-2-1H), 7.73 (d, 1H, Ph-5-1H). |
| 1.3 g | With sodium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 5h; | 0.30 g (0.0075 mol) of sodium hydroxide was added to a solution of 0.7 g (0.0037 mol) of 4-amino-2-(trifluoromethyl)benzonitrile in 40 mL of DMF, followed by addition of 1 g (0.0037 mol) of <strong>[1897-41-2]2,3,5,6-<strong>[1897-41-2]tetrachloroterephthalonitrile</strong></strong> under stirring, the mixture was stirred for 5 h after addition at room temperature. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, solid precipitated and filtered under reduced pressure to give 1.3 g of compound C-38 as yellow solid, m.p. 176-178° C. [0182] 1H-NMR (300 MHz, internal standard TMS, solvent CDCl3) delta (ppm): 6.86 (dd, 1H, Ph-6-1H), 7.16 (d, 1H, Ph-2-1H), 7.73 (d, 1H, Ph-5-1H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | With hydrogenchloride; copper(l) iodide; thionyl chloride; sodium nitrite; In water; acetone; at 0 - 20℃; for 1.0h; | Anhydrous cuprous chloride (0.3 g, 0.003 mol, 0.011 eq.) Was added to 500 ml of water, and 80 ml of dichlorosulfoxide was added dropwise under an ice-water bath, and rt overnight to obtain solution a;4-amino-2- (trifluoromethyl) benzonitrile (50.0 g, 0.269 mol, 1.0 eq.)Add 260ml of concentrated hydrochloric acid and 50ml of acetone in an ice water bath.Add sodium nitrite (20.4g, 0.296mol,1.1eq.) Dissolved in 20ml of water, stirred at 0 C for 30min,Get reaction solution a;Then add the reaction solution a dropwise to the solution a, and react at room temperature for 30 minutes.TLC monitors for complete response. |

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