Structure of 676134-68-2
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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. : | 676134-68-2 |
Formula : | C9H7BrO2 |
M.W : | 227.05 |
SMILES Code : | O=C1COCC2=C1C=C(Br)C=C2 |
MDL No. : | MFCD09744079 |
InChI Key : | KOROTCDTJPLXMA-UHFFFAOYSA-N |
Pubchem ID : | 45489802 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 48.27 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.02 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.84 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.01 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.5 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.08 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.09 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.78 |
Solubility | 0.379 mg/ml ; 0.00167 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.01 |
Solubility | 2.2 mg/ml ; 0.00971 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.72 |
Solubility | 0.0437 mg/ml ; 0.000192 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 |
-6.38 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) |
2.13 |
* 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 |
---|---|---|
86% | With methanol; at 20℃; | Step Two; 6-Bromo-isochroman-4-one; 0 Bt . COoH i AD) i . Br C02H 1. Ac2O 0 i OC02H 2. Basic Resin i O A solution of Bromo-2-carboxymethoxymethyl-benzoic acid in acetic anhydride (350 mL) containing potassium acetate (170 g) was heated at reflux for 2 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure and the residue partitioned between ethyl acetate and water. The phases were separated and the aqueous phase extracted with ethyl acetate. The combined ethyl acetate phase was then washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated to yield a red semi-solid. Purification by flash column chromatography over silica (85 : 15 hexanes/ethyl acetate) gave the enol acetate (7.59 g, 29% for three steps) as a golden syrup : 1H NMR (300 MHz, CDC13) 8 7.37 (dd, J = 8.2, 1.9 Hz, 1H), 7.19 (d, J = 1.9 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 5.04 (s, 2H), 2.29 (s, 3H). Unactivated Dowex 500A OH anion exchange resin (1 g) added in one portion to a solution of the acetate enol acetate (5.95 g, 22.11 mmol) in methanol (50 mL) and the reaction mixture stirred at room temperature overnight. The reaction mixture was gravity filtered and the resin washed with fresh methanol. The combined filtrate was then concentrated under reduced pressure to yield 6-Bromo- isochroman-4-one (4.32 g, 86%) as a yellow oil, which solidified on standing |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium tetrahydroborate; In ethanol; water; at 0 - 20℃; for 2.0h; | Step Three; 6-Bromo-isochroman-4-ol; A solution of sodium borohydride (300 mg, 7.93 mmol) dissolved in a minimum amount of ice cold water was added dropwise at 0 C to a solution of 6-Bromo-isochroman-4-one (1.49 g, 6.56 mmol) in absolute ethanol (27.0 mL). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The phases were separated and the organic phase washed with water and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield 6-Bromo-isochroman-4-ol (1.44 g, 95%) as a white solid |
95% | With sodium tetrahydroborate; In ethanol; at 0 - 20℃; for 2.0h; | A solution of sodium borohydride (300 mg, 7.93 mmol) in a minimum amount of ice cold water was added dropwise at 0 C to a solution of 6- bromo-isochromen-4-one (1.49 g, 6.56 mmol) in absolute ethanol (27.0 mL). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The phases were separated and the organic phase was washed with water and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield 6-Bromo- isochromen-4-ol (1.44 g, 95%) as a white solid :'H NMR (300 MHz, CDCl3) No. 7.40 (dd, J= 8.3, 1.8 Hz, 1H), 7.30 (d, J= 8.3 Hz, 1H), 7.15 (d, J= 1.8 Hz, 1H), 4.63 (ABq, J= 15.3 Hz, 2H), 4.49 (d, J= 8.6 Hz, 1H), 4.07 (dd, J= 12.0, 2.8 Hz, 1 H), 3.83 (dd, J = 12.0, 2.8 Hz, 1 H) 2. 60 (d, J = 9.2 Hz, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With Dowex 500A; In methanol; at 20℃; | A solution of bromo-2-carboxymethoxymethyl-benzoic acid in acetic anhydride (350 mL) containing potassium acetate (170 g) was heated at reflux for 2 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure and the residue partitioned between ethyl acetate and water. The phases were separated and the aqueous phase extracted with ethyl acetate. The combined organic phase was then washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated to yield a red semi-solid. Purification by flash column chromatography over silica (85: 15 hexanes/ethyl acetate) yielded the enol acetate (7.59 g, 29% for three steps) as a golden syrup :'H NMR (300 MHz, Ceci3) 8 7.37 (dd, J= 8.2, 1.9 Hz, 1H), 7.19 (d, J= 1.9 Hz, 1H), 6.82 (d, J= 8.2 Hz, 1H), 5.04 (s, 2H), 2.29 (s, 3H). Unactivated Dowex 500A OH anion exchange resin (1 g) added in one portion to a solution of the acetate enol acetate (5.95 g, 22.11 mmol) in methanol (50 mL) and the reaction mixture stirred at room temperature overnight. The reaction mixture was gravity filtered and the resin washed with fresh methanol. The combined filtrate was then concentrated under reduced pressure to yield 6-bromo-isochromen-4- one (4.32 g, 86%) as a yellow oil, which solidified on standing :'H NMR (300 MHz, Ceci3) 8 7.90 (d, J = 8.3 Hz, 1 H), 7.56 (dd, J = 8.3, 1.7 Hz, 1 H), 7.41 (d, J = 1.7 Hz, 1 H), 4.86 (s, 2H), 4.36 (s, 2H). |
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