Structure of 352-34-1
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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. : | 352-34-1 |
Formula : | C6H4FI |
M.W : | 222.00 |
SMILES Code : | FC1=CC=C(I)C=C1 |
MDL No. : | MFCD00001052 |
InChI Key : | KGNQDBQYEBMPFZ-UHFFFAOYSA-N |
Pubchem ID : | 9605 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.07 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.85 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.64 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.29 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.94 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.58 |
Solubility | 0.0585 mg/ml ; 0.000263 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.53 |
Solubility | 0.656 mg/ml ; 0.00296 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.63 |
Solubility | 0.0516 mg/ml ; 0.000232 mol/l |
Class? Solubility class: Log S scale |
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 |
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 |
-5.62 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) |
2.16 |
* 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 potassium carbonate;copper(l) iodide; trans-N,N'-dimethylcyclohexane-1,2-diamine; In N,N-dimethyl-formamide; at 120℃; for 3h;Sealed tube; Inert atmosphere; | A mixture of lH-<strong>[192945-49-6]indazole-4-carboxylic acid methyl ester</strong> (5.0 g, 28 mmol), copper iodide (5.7 g, 3.0 mmol), potassium carbonate (4.15 g, 30.0 mmol) and 4- fluoroiodobenzene (3.47 g, 30.0 mmol) is charged in a sealed tube at room temperature. The tube is evacuated, back-filled with argon and dimethylformamide (20 mL) is added followed by rac-trans-N,N'-dimethylcyclohexane-l,2-diamine (0.93 g, 6.5 mmol). The solution is stirred at 120C for 3 hours, then cooled to room temperature and diluted with water (50 mL) and ethyl acetate (80 mL). The organic layer is separated, washed with brine (30 mL), and dried over sodium sulfate. The crude product is filtered, concentrated and purified by silica gel chromatography eluting with a gradient of 0-30% ethyl acetate in hexanes to afford l-(4-fluoro- phenyl)-lH-<strong>[192945-49-6]indazole-4-carboxylic acid methyl ester</strong>. | |
With potassium carbonate;trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; at 20 - 120℃;Inert atmosphere; sealed tube; | A mixture of lH-<strong>[192945-49-6]indazole-4-carboxylic acid methyl ester</strong> (5.0 g, 28 mmol), copper(I) iodide (5.7 g, 3.0 mmol), potassium carbonate (4.15 g, 30.0 mmol) and A- fluoroiodobenzene (3.47 g, 30.0 mmol) was charged in a sealed tube at room temperature. The tube was evacuated, back-filled with argon and dimethylformamide (20 mL) was added followed by rac-trans-N,N'-dimethylcyclohexane-l,2-diamine (0.93 g, 6.5 mmol). The solution was stirred at 120 0C for 3 hours. The solution was cooled to room temperature and diluted with water (50 mL) and ethyl acetate (80 mL). The organic layer was separated, washed with brine (30 mL), and dried over sodium sulfate. The crude product was filtered, concentrated and purified by silica gel chromatography eluting with a gradient of 0-30% ethyl acetate in hexanes to afford l-(4-fluoro-phenyl)-lH-indazole-4- carboxylic acid methyl ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;copper(l) iodide; cis-N,N'-dimethyl-1,2-diaminocyclohexane; In N,N-dimethyl-formamide; at 130.0℃; for 1.0h;microwave irradiation; | J-3 (1.50 g, 8.56 mmol) and K2CO3 (1.50 g, 10.9 mmol) in methanol (20 mL) is warmed at reflux for 5 minutes. The mixture is filtered and concentrated to provide J-4. J-4 (1.10 g, 8.26 mmol), Oil (980.0 mg, 5.15 mmol), K2CO3 (2.75 g, 19.9 mmol), N,N- dimethyl-l,2-diaminocyclohexane (150.0 muL, 0.95 mmol) and 4-fluoroiodobenzene (2.40 g, 10.8 mmol) in DMF (13 mL) is warmed at 130C in a microwave reactor. After 1 hour, the reaction is diluted with saturated aqueous NH4C1 (50 mL) and then NaHCO3 is added and the mixture is extracted with EtOAc (3 x 50 mL). The combined organic layers are washed with saturated aqueous NH4C1 (3 x 40 mL), dried over magnesium sulfate, filtered and concentrated. The residue is purified by silica gel chromatography eluting with a gradient of 0-50% EtOAc in hexanes and crystallized from ether-hexanes to provide J-6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With copper(l) iodide; potassium carbonate; (1S,2S)-N,N'-dimethyl-1,2-diaminocyclohexane; In toluene; at 110℃; for 2h; | To a solution of 1-fluoro-4-iodo-benzene (1.47 g, 6.6 mmol, 1.3 eq) and <strong>[5932-27-4]ethyl 1H-pyrazole-3-carboxylate</strong> (0.71 g, 5.1 mmol, 1 eq) in 15 mL of toluene was added CuI (0.19 g, 1.0 mmol, 0.2 eq), trans-N,-N-dimethylcyclohexane 1,2-diamine (0.4 mL, 2.5 mmol, 0.2 eq), and potassium carbonate (1.4 g, 10 mmol, 2 eq). The reaction mixture was heated at 110° C. for 2 d then filtered and concentrated. The residue was purified by silica gel column chromatography (hex:EtoAc 4:1) to afford ethyl 1-(4-fluorophenyl)pyrazole-3-carboxylate (0.92 g, 3.9 mmol, 77percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With [ruthenium(II)(eta6-1-methyl-4-isopropyl-benzene)(chloride)(mu-chloride)]2; potassium carbonate; triphenylphosphine; In benzene; at 150℃; for 24h;Sealed tube; | General procedure: In a 30-mL sealed tube, <strong>[2622-63-1]1-methyl-2-phenylbenzimidazole</strong> (1, 0.25mmol), [RuCl2(p-cymene)]2 (0.0125 mmol), Ph3P (0.075 mmol),K2CO3 (0.50 mmol), and iodoarene (0.25 mmol) were combined inanhydrous benzene (2 mL) under air. The mixture was then stirredat 150 °C for 24 h. The mixture was cooled to r.t., diluted with EtOAc, and filtered through a small pad of Celite. The filtrate was concentrated in vacuo and purified by flash chromatography (silicagel, EtOAc?hexane) to give the analytically pure 2-(biphenyl-2-yl)benzimidazoles. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In N,N-dimethyl-formamide; at 150℃; for 24h; | Chemical compound4-fluorophenol (2mmol)With the compound 4-fluoroiodobenzene (6mmol)Dissolve in N, N-dimethylformamide (20mL) solution,After adding sodium carbonate, it was stirred at 150 C for 24h.The formed compound was extracted with ethyl acetate and washed with saturated brine to obtain compound 1a |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(eta3-allyl-mu-chloropalladium(II)); silver trifluoromethanesulfonate; In 1,2-dichloro-ethane; at 80℃; under 3040.2 Torr; for 24h;Inert atmosphere; Sealed tube; Glovebox; Schlenk technique; Green chemistry; | General procedure: Under an inert nitrogen atmosphere, silver triflate (386 mg,1.5 mmol) was transferred to a Teflon sealed thick-walled 50 ml glass reaction vessel equipped with a stir bar, followed by aryl iodide (1.0 mmol), arene (2.0 mmol), DCE (4 ml) and then a freshly prepared stock solution of [Pd(allyl)Cl]2 (0.2 mg, 5 × 10?4 mmol). The vessel was closed, removed from the glovebox, evacuated and backfilled with carbon monoxide three times, and finally pressurized with 4 atm carbon monoxide. After heating at 100 °C for 24 h with stirring, the reaction was cooled to room temperature and carbon monoxide was released. The reaction mixture was filtered through Celite, eluting with dichloromethane. Saturated NaHCO3 was added and the aqueous layer was extracted with dichloromethane. The combined organic layers were concentrated in vacuo and the residue was purified by column chromatography (silica gel, gradient hexane/ethyl acetate 0 to 20percent) to afford the pure ketone product. |