Structure of 90110-98-8
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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. : | 90110-98-8 |
Formula : | C8H6BrNO |
M.W : | 212.04 |
SMILES Code : | N#CC1=CC=C(CO)C(Br)=C1 |
MDL No. : | MFCD09907613 |
InChI Key : | LMKVEJWFFPCGJC-UHFFFAOYSA-N |
Pubchem ID : | 53424368 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 44.98 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.83 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.66 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.59 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.32 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.77 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.41 |
Solubility | 0.833 mg/ml ; 0.00393 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.98 |
Solubility | 2.22 mg/ml ; 0.0105 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.17 |
Solubility | 0.143 mg/ml ; 0.000673 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 |
-6.56 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 |
0.0 |
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) |
1.89 |
* 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 |
---|---|---|
An argon flushed round-bottom flask was charged with S1 (9.9 g, 51 mmol), N-bromosuccinimide (13.6 g, 76.5 mmol), benzoyl peroxide (61 mg, 0.25 mmol), and CCl4 (250 mL). The mixture was brought to reflux for 6 hours and then filtered upon completion with CCl4 (2 x 20 mL). The resulting crude oil was suspended in dioxane:water (1:1, 300 mL) and sodium carbonate (5 g) and brought to reflux overnight. The material was extracted against EtOAc (3 x 75 mL) and concentrated to a solid 4, which was used in the next reaction without further purification.1H NMR (CDCl3, 400 MHz) delta 4.80 (s, 2H), 7.66 (q, 2H), 7.82 (s, 1H).13C NMR (CDCl3, 100 MHz) delta 64.29, 112.66, 117.27.121.88, 128.40, 131.25, 135.45, 145.18. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With sodium tetrahydroborate; In methanol; at 0 - 25℃; | A solution of <strong>[89891-69-0]3-bromo-4-formylbenzonitrile</strong> (1.0 g, 4.8 mmol) in CH3OH (30 niL) was cooled to 00C. NaBH4 (180 mg, 4.8 mmol) was added portionwise. The mixture was allowed to warm to room temperature and stirred at room temperature for 1 h. The mixture was qunched with IN HCl and concentrated under vacuum. The residue was extracted with ethyl acetate (25 mL*3). The combined organic layers were washed with brine (20 mL), dried (Na2SO4) and concentrated under vacuum to give a white solid of the desired compound (1.Og, 99percent). NMR (300 MHz, CDCl3): delta 7.82 (s, IH), 7.49-7.71 (m, 2H), 4.75 (s, 2H). LC-MS: 212 (M + I)+. |
99% | With methanol; sodium tetrahydroborate; at 0 - 20℃; | A solution of <strong>[89891-69-0]3-bromo-4-formylbenzonitrile</strong> A (1.0 g, 4.8 mmol) in CH3OH(30 niL) was cooled to 00C. NaBH4 (180 mg, 4.8 mmol) was added portionwise. The mixture was allowed to warm to room temperature and stirr at room temperature for 1 h. The mixture was qunched with IN HCl and concentrated under vacuum. The residue was extracted with ethyl acetate (25 mL*3). The combined organic layers were washed with brine (20 mL), dried (Na2SO4) and concentrated under vacuum to give a white solid of the desired compound B (1.Og, 990Zo)-1H NMR (300 MHz, CDCl3): delta 7.82 (s, IH), 7.49-7.71 (m, 2H), 4.75 (s, 2H). LC-MS: 212 (M + I)+. |
60.7% | With methanol; sodium tetrahydroborate; at 0℃; for 0.666667h; | A solution of the product of Part 3B (3.10 g, 14.7 mmol) was dissolved MeOH (74 mL) at ambient temperature then cooled to 0 °C using an ice bath. NaBH4 (0.279 g, 7.38 mmol) was then added in one portion and the resulting solution maintained 40 min at 0 °C. Dilute aqueous HCl was added to consume excess NaBH4 then all volatiles removed in vacuo. The residue was redissolved in EtOAc with transfer to a separatory funnel, successively washed with 5percent aqueous citric acid and H2O, then dried over Na2SO4, filtered and concentrated in vacuo. Purification by chromatography on silica using a step gradient from 9: 1 hexanes/EtOAc to 1 : 1 hexanes/EtOAc afforded the title compound as a white solid (1.90 g, 8.96 mmol; 60.7percent). |
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