Structure of 215800-05-8
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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. : | 215800-05-8 |
Formula : | C9H8BrN |
M.W : | 210.07 |
SMILES Code : | CC1=C(CC#N)C=CC(Br)=C1 |
MDL No. : | MFCD14582920 |
InChI Key : | JVPNKXZIJKBMDH-UHFFFAOYSA-N |
Pubchem ID : | 18414296 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 48.63 |
TPSA ? Topological Polar Surface Area: Calculated from |
23.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.12 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.63 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.82 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.82 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.27 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.73 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.14 |
Solubility | 0.153 mg/ml ; 0.00073 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.78 |
Solubility | 0.349 mg/ml ; 0.00166 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.13 |
Solubility | 0.0154 mg/ml ; 0.0000735 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-5.71 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) |
1.45 |
* 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 |
---|---|---|
In water; N,N-dimethyl-formamide; at 80℃; for 72h; | Step 3: (4-bromo-2-methylphenvD acetonitrile; KCN (1.4 eq.) was added to a stirred solution of the benzyl bromide in DMF (0.22M) and a small amount of water (1%). The suspension was stirred 72h at 80 C. The reaction was monitored by NMR of small aliquots. The final mixture was cooled down to room temperature, poured in water and extracted with Et2theta. The organic extract was washed with water (2x), brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel, eluting with Hexane/EtOAc (5 then 10%) to give the title compound III.l as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In water; N,N-dimethyl-formamide; at 0 - 20℃; | Step c intermediate 522-(4-bromo-2-methylphenyl)acetonitrilel-Bromo-4-(bromomethyl)-3-methylbenzene (13.2 g, 50.1 mmol) is dissolved in DMF (65 mL). The reaction mixture is cooled to 0-50C and NaCN (3.66 g, 74.6 mmol) is added follow by water (8 mL). The reaction is stirred overnight at room temperature and water (170 mL) is added followed by NaHCO3 sat. (130 mL) and hexane/Et2O (2:1) (150 mL). The organic phase is separated and the aqueous phase extracted with hexane / Et2O (2:1) (3 x 150 mL). The combined organic phases are washed with water (170 mL), dried over MgSO4, filtered and concentrated under reduced pressure to provide the expected product 2-(4-bromo-2-methylphenyl)acetonitrile (9.76 g, 93 %) as an orange oil. IH NMR (300 MHz, CHLOROFORM-D): delta 7.40-7.32 (2H, m), 7.23 (2H, d, /= 8.2 Hz), 3.61 (2H, s), 2.32 (3H, s). |
92.7% | In water; N,N-dimethyl-formamide; at 20℃; | To a solution of 4-bromo-1-bromomethyl-2-methyl-benzene (3.96 g, 15 mmol) dissolved in DMF (16. mL)( were, a'dd^jspdjum cyanide (0.85 g, '17.25 mmol) and waler (1.8 ml). The reaction was sti'rred for oye'rriigh't at room temperature. To the reaction was added 1 00 ml water; 80 mL saturated NaHCO3, and 100 mL EtOAc. The layers were separated, and the aqueous layer was extracted with 3 x 100 mL EtOAc. The combined organics were washed with 100 mL water, and then dried over Na2SO4. After filtering off the solids, the mother liquor was concentrated to the desired product by rotary evaporation (2.92 g, 92.7% yield). 1H NMR (400 MHz, CDCI3): 6 2.32 (2 H, s), 3.62 (1 H, s), 7.20-7.27 (1 H, m), 7.32-7.41 (1 H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrabutylammomium bromide; In dichloromethane; water; at 0 - 20℃; for 16h; | To a solution of 4-bromo- l -(bromomethyl)-2-methylbenzene 133 (3.8) in a mixture of DCM and water was added TBAB and KCN (2.94 g) at 0 C. The mixture was stirred for 16 h at room temperature. DCM was added and the mixture was washed with water and saturated aq NaHCCh. The organic layer was separated, dried over Na2S04, and concentrated under reduced pressure to afford 2-(4-bromo-2-methylphenyl)acetonitrile 134 as a brown solid (2.9 g). The compound was used in the next reaction without further purification. LCMS: m/z 210 (M+l )+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In water; N,N-dimethyl-formamide; at 20℃; for 5h;Inert atmosphere; | NaCN (2.78 g, 56.80mmol, 1.5 eq) was added to the solution of <strong>[156001-49-9]4-bromo-1-(bromomethyl)-2-methylbenzene</strong> (10.00 g, 37.80 mmol, 1.0 eq) in DMF and H20 (10:1, 110 mL) under nitrogen atmosphere and thesolution was stirred at ambient temperature for 5 h. After complete consumption of starting material, the reaction mixture was diluted with ice cold water and extracted with diethyl ether. The organic extract was then washed with water, dried over anhydrous sodium sulfate, filtered, and solvent evaporated from the filtrated under reduced pressure to afford 2-(4-bromo-2- methylphenyl)acetonitrile as off white solid (7.5 g, 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | Sodium bis(trimethylsilyl)amide solution in THF (1M, 19.5 mL, 19.5 mmol) was added dropwise to a solution of 2-(4-bromo-2-methylphenyl)acetonitrile (3.75 g, 17.85 mmol) in THF (90 mL) at 0C. After stirring for 0.5 h, the cooling bath was removed and the reaction mixture was stirred at 20C for 0.5 h. l-Iodo-2-(2-iodoethoxy)ethane (2.8 mL, 19.67 mmol) was added dropwise. The reaction mixture was stirred for 0.5 h at 20C. Sodium bis(trimethylsilyl)amide solution in THF (1M, 19.5 mL, 19.5 mmol) was added dropwise. The reaction mixture was stirred for 18 h at 20C, then quenched with saturated aqueous ammonium chloride solution (25 mL) and diluted with water (25 mL). The aqueous layer was extracted with EtOAc (3 x 50 mL). The combined organic extracts were washed with brine (50 mL) and dried over sodium sulfate, then filtered and concentrated in vacuo. The resulting brown oil was separated by flash column chromatography on silica, using a gradient of fc/7-butyl methyl ether in heptane (0-25%), to afford the title compound (2.3 g, 45%) as a yellow solid. 6n (250 MHz, CDCb) 7.47- 7.36 (m, 2H), 7.16 (d, 8.4 Hz, 1H), 4.16-4.06 (m, 2H), 4.06-3.91 (m, 2H), 2.65 (s, 3H), 2.33-2.21 (m, 2H), 2.17-1.99 (m, 2H). HPLC-MS (method 9): [M+water]+ m/z 297 and 299, RT 1.80 minutes. |
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