Structure of 103261-67-2
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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. : | 103261-67-2 |
Formula : | C10H9NO2 |
M.W : | 175.18 |
SMILES Code : | O=C(OC)C1=CC=C(C#N)C=C1C |
MDL No. : | MFCD18399110 |
InChI Key : | PDQNYPAJSAVURS-UHFFFAOYSA-N |
Pubchem ID : | 18766060 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.4 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.09 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.1 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.47 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.65 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.59 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.0 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.69 |
Solubility | 0.356 mg/ml ; 0.00203 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.17 |
Solubility | 0.119 mg/ml ; 0.000682 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.94 |
Solubility | 0.199 mg/ml ; 0.00114 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 |
-5.61 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 |
0.0 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) |
1.68 |
* 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 |
---|---|---|
100% | With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; at 20℃; for 4h; | [0131] To a solution of methyl 5-cyano-2-toluate (5.00 g, 28.6 mmol) in CCl4 (185 mL) at RT was added NBS (5.08 g, 28.6 mmol) followed by benzoyl peroxide (830 mg, 3.43 mmol). The mixture was stirred for 4 h then poured into sat. NaHCCh (aq.), and the organic layer was separated and concentrated. Ethyl acetate (EA) was added, and the solution was dried over MgSCri then filtered and concentrated to give methyl 2-(bromomethyl)-4-cyanobenzoate (7.9 g, 100% yield) as a solid. LCMS (ESI) m/z 255 [M+H] +. |
66.9% | [0510] To a solution of methyl 4-cyano-2-methylbenzoate (4.0 g, 22.83 mmol) in CCl4 (150 mL) was added NBS (4.88 g, 27.4 mmol) and the suspension was heated at 80C for 5 min. AIBN (1.88 g, 11.42 mmol) was added and the suspension was stirred at 80C for 16 hrs, cooled to rt and filtered. The filtrate was concentrated providing the crude product, which was purified on silica gel with EA/petroleum ether from 0% to 5% providing methyl 2-(bromomethyl)-4-cyanobenzoate (3.84 g, 66.9% yield) as a white solid | |
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; | Reference Example 21 Methyl 2-bromomethyl-4-cyanobenzoate 1.0 g of benzoyl peroxide and 8.0 g of N-bromosuccinimide were added to 7.5 g of methyl 4-cyano-o-toluate obtained in Reference example 20 dissolved in 50 ml of carbon tetrachloride and the mixture was refluxed under heating for 8 hours. During reflux, 3 g of N-bromosuccinimide was added to the mixture. The resulting reaction mixture was filtered and the filtrate was washed with a saturated saline solution and then dried over anhydrous sodium sulfate. The solvent was removed from the solution to obtain 20 g of a crude product of the title compound. |
With N-Bromosuccinimide; In tetrachloromethane; for 5h;Heating / reflux; | Methyl 2-(bromomethyl)-4-cyanobenzoate (3) The compound 2 (525 mg, 3 mmol) and NBS (594 mg, 3.3 mmol) in CCl4 (20 mL) were refluxed for 5 hours. The reaction was cooled to room temperature. Hexane was added into the reaction and the solid obtained was removed by filtration. The filtrate was concentrated under the reduced pressure to give the crude compound 3, which was used directly in the next step. | |
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 3h;Inert atmosphere; Reflux; | A mixture of 4-cyano-2-methyl-benzoic acid methyl ester (12.5 g,71.35 mmol), NBS (12.7 g,71.35 mmol) and di-benzoyl peroxide (BPO) (0.8 g,3.28 mmol) in CCI4 (200 mL) was heated to reflux temperature for 3 hours. After it was cooled to room temperature, the reaction mixture was filtered. The filtrate was concentrated in vacuo to give a crude product (18.2 g) which was used in the next step reaction without further purification. | |
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃; for 48h; | Step 2. methyl 2-(bromomethyl)-4-cyanobenzoate To a stirred solution of methyl 4-cyano-2-methylbenzoate (1 g, 5.7 mmol) in CCl4 (30 mL), was added NBS (1.4 g, 6.2 mmol), and catalytic AIBN. The reaction mixture was stirred for 48 h at 80 C. The reaction progress was monitored by TLC (10% EtOAc in hexanes). The reaction was cooled to room temperature and diluted with water (25 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (2*50 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, concentrated, and purified by column chromatography silica (60-120 mesh silica with 80-100% EtOAc in petroleum ether) as eluent to give the title compound as a colorless solid. 1H NMR (400 MHz, CDCl3): delta 8.05 (d, J=8.0 Hz, 1H), 7.78 (s, 1H), 7.6 (d, J=8.0 Hz, 1H), 4.9 (s, 2H), 4.0 (s, 3H). | |
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 3h;Inert atmosphere; Reflux; | A mixture of 4-cyano-2-methyl-benzoic acid methyl ester (12.5 g, 71.35 mmol), NBS (12.7 g, 71.35 mmol) and di-benzoyl peroxide (BPO) (0.8 g, 3.28 mmol) in CC14 (200 mL) was heated to reflux temperature for 3 hours. Then, it was cooled to room temperature and the reaction mixture was filtered. The filtrate was concentrated in vacuo to give a crude product (18.2 g) which was used in the next step reaction without further purification. | |
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 3h;Inert atmosphere; Reflux; | A mixture of 4-cyano-2-methyl-benzoic acid methyl ester (12.5 g,71.35 mmol), NBS (12.7 g, 71.35 mmol) and di-benzoyl peroxide (BPO) (0.8 g, 3.28 mmol) in CC14 (200 mL) was heated to reflux temperature for 3 hours. After cooling to room temperature, the reaction mixture was filtered. The filtrate was concentrated in vacuo to give a crude product (18.2g) which was used in the next step reaction without further purification. | |
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 3h;Inert atmosphere; Reflux; | A mixture of 4-cyano-2-methyl-benzoic acid methyl ester (12.5 g, 71.35 mmol), NBS (12.7 g, 71.35 mmol) and di-benzoyl peroxide (BPO) (0.8 g, 3.28 mmol) in CC14 (200 mL) was heated to reflux temperature for 3 hours. After cooling to room temperature, the reaction mixture was filtered. The filtrate was concentrated in vacuo to give a crudeproduct (18.2 g) which was used in the next step reaction without further purification. | |
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 3h;Reflux; Inert atmosphere; | TCI 2-Bromomethyl-4-cyano-benzoic acid methyl ester A mixture of 4-cyano-2-methyl-benzoic acid methyl ester (12.5 g, 71.35 mmol), NBS (12.7 g, 71.35 mmol) and di-benzoyl peroxide (BPO) (0.8 g, 3.28 mmol) in CC14 (200 mL) was heated to reflux temperature for 3 hours. After it was cooled to room temperature, the reaction mixture was filtered. The filtrate was concentrated in vacuo to give a crude product (18.2 g) which was used in the next step reaction without further purification. | |
With N-Bromosuccinimide; dibenzoyl peroxide; In 1,2-dichloro-ethane; at 80℃; for 12h; | General procedure: A mixture of methyl 5-fluoro-2-methylbenzoate (0.5 g, 3.0 mmol),NBS (0.18 g, 3.0 mmol), and di-benzoyl peroxide (BPO) (36 mg, 0.15 mmol) in 1,2-dichloroethane (5 mL) was heated at 80 C for 12 huntil all starting material was consumed. The reaction was cooled to room temperature, and the precipitated solid was removed by filtration and washed with ethers (10 mL). The filtrate was concentrated in vacuo and the residue was partitioned between 2 N NaHCO3 (15 mL) and ethers (15 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated to give a crude product (0.65 g, 89%), which was used in the next step reaction without further purification. | |
With N-Bromosuccinimide; dibenzoyl peroxide; In 1,2-dichloro-ethane; at 80℃; for 12h; | General procedure: A mixture of methyl 3-bromo-2-methylbenzoate (500 mg, 3.3 mmol), NBS (770.4 mg, 4.3 mmol), and di-benzoyl peroxide (BPO, 80.7 mg, 0.3 mmol) in 1,2-dichloroethane (10 mL) was heated at 80 C for 12 h. The reaction mixture was cooled to room temperature, and the precipitated solid was removed by filtration and washed with ethers (10 mL). The filtrate was concentrated in vacuo and the residue was partitioned between 2 N NaHCO3 (15 mL) and ethers (15 mL). The organic layer was separated, dried over NaSO4, filtered and concentrated to give a crude product (683.2 mg, 89.6%), which was used in the next step reaction without further purification. |
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