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Structure of 149489-32-7
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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. : | 149489-32-7 |
Formula : | C6H5ClFN |
M.W : | 145.56 |
SMILES Code : | FC1=CC=CN=C1CCl |
MDL No. : | MFCD11520697 |
InChI Key : | VACDDNDGSMRWPV-UHFFFAOYSA-N |
Pubchem ID : | 15133602 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H314 |
Precautionary Statements: | P260-P264-P270-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501 |
Class: | 8 |
UN#: | 3265 |
Packing Group: | Ⅱ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 33.96 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.72 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.38 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.23 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.58 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.75 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.93 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.04 |
Solubility | 1.33 mg/ml ; 0.00914 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.25 |
Solubility | 8.11 mg/ml ; 0.0557 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.3 |
Solubility | 0.0726 mg/ml ; 0.000499 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 |
-6.21 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 |
2.0 |
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) |
1.66 |
* 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 |
---|---|---|
80% | With thionyl chloride; In dichloromethane; at 0℃; for 1h; | Preparation 60; 2-Chloromethyl-3-fluoro-pyridine EPO <DP n="167"/>Dissolve <strong>[31181-79-0](3-fluoro-pyridin-2-yl)-methanol</strong> (215 mg, 1.69 mmol) in dichloromethane (10 mL) and cool to 0 0C. Add thionyl chloride (160 muL, 2.20 mmol) and stir the reaction for one hour. Add dichloromethane (50 mL) and stir the reaction with saturated aqueous sodium bicarbonate (2 x 40 mL) and brine (2 x 40 mL). Separate and dry the organic portion over magnesium sulfate, filter, and concentrate under reduced pressure to provide 198 mg (80%) of product, which is used without further purification. MS: m/z 146, 148 [C6H5ClFN + I]+; 1H NMR (300 MHz, CDCl3): delta 8.41-8.44 (m, IH), 7.41-7.47 (m, IH), 7.28-7.34 (m, IH), 4.75 (d, J = 2.0 Hz, 2H); 19F NMR (282 MHz, CDCl3): delta -123.8. |
66.5% | With thionyl chloride; In dichloromethane; at 0 - 20℃; for 2h; | To a solution of <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (1.8 g, 13.8 mmol, 1 equiv) in DCM( 20 mL) was added SOCh ( 2.5 mL, 35 mmol, 2.5 equiv) dropwise at 0C. The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated aqueous NaHCCb solution and extracted with DCM (3 * 20 mL). The combined organic layers were dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by column chromatography (eluted with PE/EtOAc = 5/1) to afford the title compound 2-(chloromethyl)-3-fluoropyridine (1.33 g, 66.5% yield). LC-MS: m/z 146.0, 148.0 (M+H) + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 60℃; | Example 126A 5-Chloro-3-[(3-fluoropyridin-2-yl)methoxy]-2-nitropyridine 20.0 g (114.6 mmol) of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong>e from Example 15A and 56.0 g (171.9 mmol) of caesium carbonate were initially charged in 319 ml of DMF. 17.51 g (120.3 mmol) of 2-(chloromethyl)-3-fluoropyridine (commercially available; additionally described in: K. Weidmann et al. Journal of Medicinal Chemistry 1992, 35, 438-450; U.S. Pat. No. 5,593,993, 1997; WO2007/2181 A2, 2007) were added, and the reaction mixture was stirred at RT overnight. 6.0 g (41.2 mmol) of 2-(chloromethyl)-3-fluoropyridine were added, and the mixture was stirred at RT for 24 h. Another 6.0 g (41.2 mmol) of 2-(chloromethyl)-3-fluoropyridine and 5.0 g (15.3 mmol) of caesium carbonate were then added, and the mixture was stirred at 60 C. for 12 h. The reaction mixture was added carefully to 2.3 l of 0.5 M aqueous hydrochloric acid. The mixture was extracted three times with in each case 500 ml of ethyl acetate. The combined organic phases were washed with 500 ml of saturated aqueous sodium chloride solution, dried and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate gradient: 9/1 to 7/3). This gave 29.8 g (92% of theory) of the target compound. LC-MS (Method 1): Rt=0.94 min. MS (ESIpos): m/z=284 (M+H)+. 1H-NMR (400 MHz, DMSO-d6): delta=5.59 (d, 2H), 7.53-7.60 (m, 1H), 7.80-7.87 (m, 1H), 8.26 (d, 1H), 8.40-8.47 (m, 2H). |
92% | With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 60℃; | 20.0 g (114.6 mmol) of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> from Example 38A and 56.0 g (171.9 mmol) of caesium carbonate were initially charged in 319 ml of DMF. 17.51 g (120.3 mmol) of 2-(chloromethyl)-3-fluoropyridine (commercially available; additionally described in: K. Weidmann et al. Journal of Medicinal Chemistry 1992, 35, 438-450; U.S. Pat. No. 5,593,993, 1997; WO2007/2181 A2, 2007) were added and the reaction mixture was stirred at RT overnight. 6.0 g (41.2 mmol) of 2-(chloromethyl)-3-fluoropyridine were added and the mixture was stirred at RT for 24 h. Subsequently, another 6.0 g (41.2 mmol) of 2-(chloromethyl)-3-fluoropyridine and 5.0 g (15.3 mmol) of caesium carbonate were added and the mixture was stirred at 60 C. for 12 h. The reaction mixture was added carefully to 2.3 l of 0.5 M of aqueous hydrochloric acid. The mixture was extracted three times with in each case 500 ml of ethyl acetate. The combined organic phases were washed with 500 ml of saturated aqueous sodium chloride solution, dried and concentrated under reduced pressure. The crude product was purified by means of silica gel chromatography (mobile phase: cyclohexane/ethyl acetate gradient: 9/1 to 7/3). This gave 29.8 g (92% of theory) of the target compound. LC-MS (Method 1): Rt=0.94 min. MS (ESIpos): m/z=284 (M+H)+. 1H-NMR (400 Mhz, DMSO-d6): delta=5.59 (d, 2H), 7.53-7.60 (m, 1H), 7.80-7.87 (m, 1H), 8.26 (d, 1H), 8.40-8.47 (m, 2H). |
29.8 g | With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 60℃; | Example 28A 5-Chloro-3-[(3-fluoropyridin-2-yl)methoxy]-2-nitropyridine 20.0 g (114.6 mmol) of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> from Example 27A and 56.0 g (171.9 mmol) of caesium carbonate were initially charged in 319 ml of DMF. 17.51 g (120.3 mmol) of 2-(chloromethyl)-3-fluoropyridine (commercially available; additionally described in: K. Weidmann et al. Journal of Medicinal Chemistry 1992, 35, 438-450; U.S. Pat. No. 5,593,993, 1997; WO2007/2181 A2, 2007) were added and the reaction mixture was stirred at RT overnight. 6.0 g (41.2 mmol) of 2-(chloromethyl)-3-fluoropyridine were added and the mixture was stirred at RT for 24 h. Subsequently, another 6.0 g (41.2 mmol) of 2-(chloromethyl)-3-fluoropyridine and 5.0 g (15.3 mmol) of caesium carbonate were added and the mixture was stirred at 60 C. for 12 h. The reaction mixture was added carefully to 2.3 l of 0.5 M aqueous hydrochloric acid. The mixture was extracted three times with in each case 500 ml of ethyl acetate. The combined organic phases were washed with 500 ml of saturated aqueous sodium chloride solution, dried and concentrated under reduced pressure. The crude product was purified by means of silica gel chromatography (mobile phase: cyclohexane/ethyl acetate gradient: 9/1 to 7/3). This gave 29.8 g (92% of theory) of the target compound. LC-MS (Method D): Rt=0.94 min. MS (ESIpos): m/z=284 (M+H)+. 1H-NMR (400 MHz, DMSO-d6): delta=5.59 (d, 2H), 7.53-7.60 (m, 1H), 7.80-7.87 (m, 1H), 8.26 (d, 1H), 8.40-8.47 (m, 2H). |
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