Structure of 199786-58-8
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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. : | 199786-58-8 |
Formula : | C7H6BrIO |
M.W : | 312.93 |
SMILES Code : | OCC1=CC(Br)=CC=C1I |
MDL No. : | MFCD09745850 |
Boiling Point : | No data available |
InChI Key : | LBMPOOHWJBYWPY-UHFFFAOYSA-N |
Pubchem ID : | 15339730 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 52.99 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.13 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.38 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.39 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.17 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.32 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.68 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.66 |
Solubility | 0.0688 mg/ml ; 0.00022 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.45 |
Solubility | 1.12 mg/ml ; 0.00358 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.01 |
Solubility | 0.0304 mg/ml ; 0.0000973 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) |
Yes |
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 |
-6.52 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.9 |
* 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 |
---|---|---|
98% | With dipyridinium dichromate; In dichloromethane; at 20℃; for 4h;Inert atmosphere; | To a stirred solution of PDC (11.0 g, 0.0288 mol) in CH2Cl2 (60 mL) was added a solution of 11 (4.50 g, 0.0144 mol) in CH2Cl2 (20 mL). The mixed content was stirred for 4 h at rt. The solvent was then removed under vacuum to give the crude product of 12, which was purified by silica flash column chromatography (hexanes/CH2Cl2, 7:3) to give compound 12 (4.40 g, 0.0142 mol, 98%) as a white solid. |
93% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine; In dichloromethane; at -70 - -10℃; for 1.25h;Inert atmosphere; | A solution of oxalyl chloride (1 .99 mL, 23.04 mmol, 1 .6 equiv) in DCM (25 mL) was cooled to -70C and DMSO (2.44 mL, 34.5 mmol, 2.4 equiv) in DCM (25 mL) was added at -65C to -70C. The reaction mixture stirred for 10 minutes under nitrogen atmosphere at - 70C and then (5-bromo-2-iodophenyl)methanol (4.55 g, 14.4 mmol, 1 .0 equiv) in DCM (100 mL) was added. The reaction mixture was stirred at -65C for 15 minutes and triethylamine (10 mL, 72 mmol, 5.0 equiv) was added. The reaction mixture was allowed to warm to -10C and stir for 1 h. Water (40 mL) was added and the reaction mixture was allowed to warm to room temperature. The organic layer was separated and evaporated to obtain 5-bromo-2-iodobenzaldehyde (4.2 g, 93 %) as white solid. 1H NMR (400 MHz.CDCb) δ ppm 7.45 (d, J=7.6 Hz, 1 H), 7.81 (d, J=1 1 .6 Hz, 1 H), 7.98 (d, J=1 .6 Hz, 1 H), 9.97 (s, 1 H). |
A solution of oxalyl chloride (1.53 g, 0.012 mol) in CH2Cl2 (15 ML) was cooled to -70 C., and DMSO (1.41 g, 0.018 mol) in CH2Ck (15 ML) was added at -65 to -70 C. The mixture was stirred under nitrogen for 10 minutes at -70 C. and then treated with the product from Example 62B (2.35 g, 7.5 mmol) in 60 ML CH2Cl2.The slurry was stirred at -65 C. for 15 minutes and treated with triethylamine (3.8 g, 0.037 mol).The mixture was allowed to warm to -10 C. over 1 hour.The mixture was treated with 20 ML of water and allowed to warm to room temperature.The organic layer was separated and concentrated to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.97 (s, 1H), 7.97 (d, J=4 Hz, 1H), 7.79 (d, J=8 Hz, 1H), 7.40 (dd, J=4, 8 Hz, 1H). MS (DCl/NH3) [M+NH4]+ at 328. |
With oxalyl dichloride; dimethyl sulfoxide; triethylamine; In dichloromethane; at -70 - -10℃; for 1.25h; | A solution of oxalyl chloride (1.53 g, 0.012 mol) in CH2Cl2 (15 mL) was cooled to -70 C., and DMSO (1.41 g, 0.018 mol) in CH2Cl2 (15 mL) was added at -65 to -70 C. The mixture was stirred under nitrogen for 10 minutes at -70 C. and then treated with the product from Example 15B (2.35 g, 7.5 mmol) in 60 mL CH2Cl2. The slurry was stirred at -65 C. for 15 minutes and treated with triethylamine (3.8 g, 0.037 mol). The mixture was allowed to warm to -10 C. over 1 hour. The mixture was treated with 20 mL of water and allowed to warm to room temperature. The organic layer was separated and concentrated to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.97 (s, 1H), 7.97 (d, J=4 Hz, 1H), 7.79 (d, J=8 Hz, 1H), 7.40 (dd, J=4, 8 Hz, 1H). MS (DCl/NH3) [M+NH4]+ at 328. | |
Example 15C 5-Bromo-2-iodobenzaldehyde A solution of oxalyl chloride (1.53 g, 0.012 mol) in CH2Cl2 (15 mL) was cooled to -70 C., and DMSO (1.41 g, 0.018 mol) in CH2Cl2 (15 mL) was added at -65 to -70 C. The mixture was stirred under nitrogen for 10 minutes at -70 C. and then treated with the product from Example 15B (2.35 g, 7.5 mmol) in 60 mL CH2Cl2. The slurry was stirred at -65 C. for 15 minutes and treated with triethylamine (3.8 g, 0.037 mol). The mixture was allowed to warm to -10 C. over 1 hour. The mixture was treated with 20 mL of water and allowed to warm to room temperature. The organic layer was separated and concentrated to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.97. (s, 1H), 7.97 (d, J=4 Hz, 1H), 7.79 (d, J=8 Hz, 1H), 7.40 (dd, J=4, 8 Hz, 1H). MS (DCl/NH3) [M+NH4]+ at 328. | ||
With dipyridinium dichromate; In dichloromethane; at 20℃; for 4h; | The compound was synthesized according to the published procedure. [Zhou, N.; Wang, L.; Thompson, D. W.; Zhao, Y. Org. Lett. 2008, 10 (14), 3001-3004] Compound L15 and pyridinium dichromate (7.2 g, 19.2 mmol, 2 eq.) were dissolved in dry dichloromethane (40 ml) and the mixture was stirred at room temperature for 4 hours. The mixture was filtered through celite, washed with diethyl ether and solvents were evaporated. The solid was adsorbed on silica gel in a mixture of cyclohexane/acetone and it was purified by flash column chromatography on silica gel (cyclohexane to 20% ethyl acetate modified with 10% methanol (v/vi)), yielded 2.3 g (77%) of the title compound as a white solid (85% NMR purity). 1H NMR (401 MHz, Chloroform-d) δ 9.99 (s, 1H), 7.99 (d, J= 2.5 Hz, 1H), 7.81 (d, J= 8.4 Hz, 1H), 7.41 (dd, J= 8.4, 2.5 Hz, 1H). 13C NMR (101 MHz, Chloroform-d) δ 194.45, 141.95, 138.37, 136.47, 133.24, 123.63, 98.39. MS (CI-QMS) m/z: [M + H]+ calcd for C7H5BrIO, 310.9; found, 310.9. |
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