Structure of 196799-45-8
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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. : | 196799-45-8 |
Formula : | C9H8O2 |
M.W : | 148.16 |
SMILES Code : | O=CC1=C(OCC2)C2=CC=C1 |
MDL No. : | MFCD06200853 |
InChI Key : | CLXXUGOCVBQNAI-UHFFFAOYSA-N |
Pubchem ID : | 2795018 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-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 | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.17 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.77 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.39 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.43 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.05 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.65 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.66 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.97 |
Solubility | 1.58 mg/ml ; 0.0107 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.55 |
Solubility | 4.22 mg/ml ; 0.0285 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.62 |
Solubility | 0.358 mg/ml ; 0.00242 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 |
-6.22 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 |
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) |
1.78 |
* 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 |
---|---|---|
With hydrogenchloride; dmap; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; | EXAMPLE 206 STR276 2,3-Dihydrobenzofuran-7-carboxaldehyde A solution of 2,3-dihydrobenzofuran-7-carboxylic acid (1.0 g, 6.09 mmol, 1.0 equiv.), dimethylmethoxyamine hydrochloride (654 mg, 6.7 mmol, 1.1 equiv.), diisopropylethylamine (DIEA) (2.35 ml, 13.4 mmol, 2.2 equiv.), benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP) (3.48 g, 6.7 mmol, 1.1 equiv.) and 4-dimethylaminopyridine (DMAP) (74 mg, 0.67 mmol, 0.1 equiv.) in anhydrous THF (20 ml) was stirred for 18 hr under argon. The reaction mixture was then diluted with EtOAc (100 ml) and washed with aqueous sat. NaHCO3 (2*150 ml) and aqueous 1N HCl (2*150 ml), the oragnic layer was dried over MgSO4, filtered and solvent removed. yield: 1.06 mg, 84%. LS-MS calcd 207, found 208. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With manganese(IV) oxide; In toluene; at 60℃; for 3h; | A mixture of <strong>[151155-53-2](2,3-dihydrobenzofuran-7-yl)methanol</strong> (9.76 g, 64.99 mmol) and manganese dioxide (45.2 g, 519.93 mmol) in toluene (250 mL) was stirred at 60C for 3 hr. The manganese dioxide was filtered off, and the filtrate was concentrated under reduced pressure. The precipitate was collected by filtration and washed with cooled hexane to give 2,3-dihydrobenzofuran-7-carbaldehyde (7.43 g, 50.1 mmol, 77%) as a pale yellow solid. |
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 2h; | [00323] 2,3-Dihydrobenzofuran-7-carboxylic acid (820 mg, 5 mmol) was dissolved inTHF (10 mL). To the solution was added TEA (0.7 mL, 5 mmol) and methylchloroformate (0.43 mL, 5 mmol). The solution was stirred for 0.5 hour. The white precipitates were removed by filtration, the filtrate was added to a solution OfNaBH4 (437 mg, 12.5 mmol) in H2O (5 mL). The resulting solution was stirred overnight. The reaction mixture was neutralized with 2 M aqueous HCl solution and then extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The crude alcohol was dissolved in DCM. To the solution was added PCC (1.83 g, 7.5 mmol). The mixture was stirred for 2 hours at room temperature and diluted with diethyl ether, then ether layers were decanted. Combined organic layer was filtered though a layer of Celite. The filtrate was concentrated to give crude product. The crude was purified from column EPO <DP n="307"/>with 10% EtOAc/hexane to afford 450 mg of 2,3-dihydrobenzofuran-7-carbaldehyde as a slightly yellow solid. HPLC 4.3 min. | |
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 2h; | [0359] 2,3-Dihydrobenzofuran-7-carboxylic acid (820 mg, 5 mmol) was dissolved inTHF (10 rtiL). To the solution was added TEA (0.7 mL, 5 mmol) and methylchloroformate (0.43 mL, 5 mmol). The solution was stirred for 0.5 hour. The white precipitates were removed by filtration, the filtrate was added to a solution OfNaBH4 (437 mg, 12.5 mmol) in H2O (5 mL). The resulting solution was stirred overnight. The reaction mixture was neutralized with 2 M aqueous HCl solution and then extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The crude alcohol was dissolved in DCM. To the solution was added PCC (1.83 g, 7.5 mmol). The mixture was stirred for 2 hours at room temperature and diluted with diethyl ether, then ether layers were decanted. Combined organic layer was filtered though a layer of Celite. The filtrate was concentrated to give crude product. The crude was purified from column with 10% EtOAc/hexane to afford 450 mg of 2,3-dihydrobenzofuran-7-carbaldehyde as a slightly yellow solid. HPLC 4.3 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2,3-Dihydro-benzofuran-7-carbaldehyde (1.50 g, 10.20 mmol) was dissolved in ether, then cooled to 0 C., NaBH4 (400 mg, 10.57 mmol) in MeOH (5.00 mL) was added. The resulting reaction mixture was stirred for 30 min, then saturated ammonium chloride was added. The mixture was extracted with ether, and the combined organic phases were washed with brine, then dried over magnesium sulfate and concentrated to afford the desired alcohol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tetrahydroborate; triethanolamine; 4,5-dichloro-1-phenylpyridazin-6-one; In tetrahydrofuran; water; ethyl acetate; | Preparation of 2,3-dihydrobenzofuran-7-carbaldehyde 2,3-Dihydrobenzofuran-7-carboxylic acid (820 mg, 5 mmol) was dissolved in THF (10 mL). To the solution was added TEA (0.7 mL, 5 mmol) and methylchloroformate (0.43 mL, 5 mmol). The solution was stirred for 0.5 hr. The white precipitates were removed by filtration, the filtrate was added to a solution of NaBH4 (437 mg, 12.5 mmol) in H2O (5 mL). The resulting solution was stirred overnight. The reaction mixture was neutralized with 2 M aqueous HCl solution and then extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The crude alcohol was dissolved in DGM. To the solution was added PCC (1.83 g, 7.5 mmol). The mixture was stirred for 2 hrs at room temperature and diluted with diethyl ether, then ether layers were decanted. Combined organic layer was filtered though a layer of Celite. The filtrate was concentrated to give crude product. The crude was purified from column with 10% EtOAc/hexane to afford 450 mg of 2,3-dihydrobenzofuran-7-carbaldehyde as a slightly yellow solid. HPLC 4.3 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | 7-Bromo-2,3-dihydrobenzofuran (74A) under nitrogen protection(2.0g, 10.05mmol) dissolved in tetrahydrofuran(20 mL), cooled to -78 C, n-butyl lithium (4.5 mL, 11.05 mmol)Add dropwise to the reaction, and add the stirring reaction for 0.5 hours.Further, N,N-dimethylformamide (1.1 g, 15.07 mmol) was added dropwise to the reaction.Continue to react for 1 hour. The reaction solution was quenched with saturated aqueous ammonium chloride (50 mL).The aqueous phase was extracted with ethyl acetate (30 mL×3).Wash with saturated sodium chloride solution (50 mL), dry over anhydrous sodiumAfter the filtrate is concentrated, the crude product is subjected to column chromatography.(Petroleum ether/ethyl acetate (v/v) = 10:1 to 4:1) to give an oily liquid 2,3-dihydrobenzofuran-7-carbaldehyde (74B)(1.4 g, yield: 94%). |
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