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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 328-72-3
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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. : | 328-72-3 |
Formula : | C8H3ClF6 |
M.W : | 248.55 |
SMILES Code : | FC(C1=CC(C(F)(F)F)=CC(Cl)=C1)(F)F |
MDL No. : | MFCD01861848 |
InChI Key : | OXMBWPJFVUPOFO-UHFFFAOYSA-N |
Pubchem ID : | 2769405 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H315-H319-H225 |
Precautionary Statements: | P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅲ |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.46 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.34 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.88 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
6.68 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.56 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.68 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.62 |
Solubility | 0.00597 mg/ml ; 0.000024 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.62 |
Solubility | 0.00603 mg/ml ; 0.0000243 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.79 |
Solubility | 0.00401 mg/ml ; 0.0000161 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) |
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 |
-4.35 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
1.0 |
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 |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.57 |
* 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 chlorosulfonic acid; iodine; chlorine; | EXAMPLE 3 STR6 130 parts of chlorosulfonic acid are introduced, at room temperature, into a reaction vessel, and 42.8 parts of 1,3-bis-(trifluoromethyl)-benzene and 2 parts of iodine are added. The suspension is cooled to 0 and 30 parts of chlorine are introduced in the course of 5 hours at 0 to 5. The suspension is then poured out onto ice and the organic phase is separated from the aqueous phase. The organic phase is washed neutral with ice-cold water and is dried over calcined sodium sulfate. 38 parts of 5-chloro-1,3-bis-(trifluoromethyl)-benzene, of boiling point 111 to 112, are obtained. Analysis for chlorine - calculated: 14.28%, found: 14.02%. Analysis for fluorine - calculated: 45.8%, found: 45.4%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With trichloroisocyanuric acid; bromine; In tetrachloromethane; at -10 - 100℃; for 18h;Photolysis; | General procedure: Round bottom flask equipped with Dimroth condenser (chilled to -10 C) was charged with arenecarboxylic acid (1.8 mmol), chloroisocyanurate, brominating agent and solvent (8 mL). The mixture was magnetically stirred and heated in an oil bath under 3 W LED warm-white lamp irradiation (LL) or under fluorescent room light irradiation (FL). The cooled reaction mixture was filtered through a short silica gel pad, washed with 1 M aq Na2SO3, dried over Na2SO4, filtered and the solvent was removed by distillation. In case of volatile product the yield was determined by gas chromatography (GC) with internal standard. The results are presented in Table 7 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Example 8 As Example 3, but 24.9 g of <strong>[328-72-3]3,5-(bistrifluoromethyl)chlorobenzene</strong> were reacted. 15.5 g of 3,5-(bistrifluoromethyl)benzonitrile were isolated as a colorless liquid (65% of theory). | |
In butanone; | STR7 Preparation of 3,5-bis-(trifluoromethyl)-benzonitrile By the method of Example 3, 124 g of 1-chloro-3,5-bis-(trifluoromethyl)-benzene in 120 ml of ethyl methyl ketone gave 61.4 g (51.2% of theory) of 3,5-bis-(trifluoromethyl)-benzonitrile (b.p.45 mbar: 88 C.). After 20 hours, the conversion was approximately 60%. 4.5% of coupling products had formed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With NBu4Br;palladium diacetate; In ISOPROPYLAMIDE; water; | Example 16 Synthesis of 3,5-bis(trifluoromethyl)cinnamonitrile 0.382 g (7.2 mmol) of acrylonitrile, 38.7 mg (120 mumol) of NBu4Br, 6.7 mg (30 mumol) of palladium acetate and 26.7 mg (120 mumol) of phenyldi(t-butyl)phosphine are weighed into a Schlenk vessel. 1.49 g (6 mmol) of <strong>[328-72-3]3,5-bis(trifluoromethyl)chlorobenzene</strong> and 1.53 ml (7.2 mmol) of dicyclohexylmethylamine and also 3.5 ml of dimethylacetamide are then added. The Schlenk vessel is placed in a heating bath at 130 C. and the contents are stirred. After 4 hours, the contents are poured into 30 ml of water and the product is extracted by shaking with t-butyl methyl ether. After drying the organic phase over MgSO4, the solvent is removed under reduced pressure and the product is isolated. Orange oil, yield: 69%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With NBu4Br;palladium diacetate; In ISOPROPYLAMIDE; water; | Example 9 Synthesis of 3,5-bis(trifluoromethyl)cinnamide (Method I) 0.512 g (7.2 mumol) of acrylamide, 38.7 mg (120 mumol) of NBu4Br, 6.7 mg (30 mumol) of palladium acetate and 26.7 mg (120 mumol) of phenyldi(t-butyl)phosphine are weighed into a Schlenk vessel. 1.49 g (6 mmol) of <strong>[328-72-3]3,5-bis(trifluoromethyl)chlorobenzene</strong> and 1.53 ml (7.2 mmol) of dicyclohexylmethylamine and also 3.5 ml of dimethylacetamide are then added. The Schlenk vessel is placed in a heating bath at 130 C. and the contents are stirred. After 4 hours, the contents are poured into 30 ml of water, the solid product is filtered off with suction and washed with about 50 ml of water. Light-grey solid, yield after drying: 1.63 g (96% of theory). | |
With NBu4Br;palladium diacetate; In ISOPROPYLAMIDE; | Example 10 Synthesis of 3,5-bis(trifluoromethyl)cinnamide (Method II) 0.181 g (2.55 mmol) of acrylamide, 9.7 mg (30 mumol) of NBu4Br, 0.675 mg (3 mumol) of palladium acetate and 2.67 mg (12 mumol) of phenyldi(t-butyl)phosphine are weighed into a Schlenk vessel. 0.542 g (3 mmol) of <strong>[328-72-3]3,5-bis(trifluoromethyl)chlorobenzene</strong> and 0.637 ml (3 mmol) of dicyclohexylmethylamine and also 2.5 ml of dimethylacetamide are then added. The Schlenk vessel is placed in a heating bath at 130 C. and the contents are stirred. After 3 hours, the yield is determined by means of HPLC: 99% (TON=723, TOF=241/h). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With NBu4Br;palladium diacetate; In ISOPROPYLAMIDE; water; | Example 13 Synthesis of Methyl 3,5-bis(trifluoromethyl)cinnamate 0.619 g (7.2 mmol) of methyl acrylate, 38.7 mg (120 mumol) of NBu4Br, 6.7 mg (30 mumol) of palladium acetate and 26.7 mg (120 mumol) of phenyldi(t-butyl)phosphine are weighed into a Schlenk vessel. 1.49 g (6 mmol) of <strong>[328-72-3]3,5-bis(trifluoromethyl)chlorobenzene</strong> and 1.53 ml (7.2 mmol) of dicyclohexylmethylamine and also 3.5 ml of dimethylacetamide are then added. The Schlenk vessel is placed in a heating bath at 130 C. and the contents are stirred. After 4 hours, the contents are poured into 30 ml of water and the product is extracted by shaking with t-butyl methyl ether. After drying the organic phase over MgSO4, the solvent is removed under reduced pressure and the product is isolated. Yellowish, crystalline solid, yield: 1.34 g (97% of theory). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; bis(eta3-allyl-mu-chloropalladium(II)); In 1,3,5-trimethyl-benzene; at 0 - 145℃; for 20.25h;Inert atmosphere; Large scale; | 50L clean glass vessel, dried in a stream of nitrogen was added 20kg mesitylene, open stirring, degassed with nitrogen purge 15min, was added under stirring 5.0kg3,5- bis-trifluoromethyl-chlorobenzene (20.1mol), 2.5kg cyano acetate (21.0mol), 8.0g of allyl palladium chloride dimer (0.0217mol, 0.22mol%), 27g2- dicyclohexyl phosphino-2 ', 6'-dimethoxy biphenyl (0.066mol , 0.66mol%); under nitrogen flow, the temperature of the reaction system was gradually raised to 145 20h the reaction, the reaction system was then lowered to room temperature, the reaction was filtered to remove sodium chloride, and the filtrate recovery spin dry mesitylene, and concentrated to give 5.5kg the residue is 2- (3,5-bis-trifluoromethylphenyl) acetonitrile crude product, detecting the GC purity was 92%, a yield of 81%. |
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