Structure of 533-58-4
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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. : | 533-58-4 |
Formula : | C6H5IO |
M.W : | 220.01 |
SMILES Code : | OC1=C(I)C=CC=C1 |
MDL No. : | MFCD00013963 |
InChI Key : | KQDJTBPASNJQFQ-UHFFFAOYSA-N |
Pubchem ID : | 10784 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.73 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.65 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.41 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.39 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.23 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.43 |
Solubility | 0.082 mg/ml ; 0.000373 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.73 |
Solubility | 0.414 mg/ml ; 0.00188 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.78 |
Solubility | 0.366 mg/ml ; 0.00166 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 |
-5.76 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) |
1.85 |
* 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 sulfuryl dichloride; diisopropylamine; In toluene; at 70.0℃; | Synthesis of 2-( ( 2 '-C hloro-6 '-( pyridin-4-yl)biphenyl-4-yloxy)methyl)alpha uinoline (Example 382)2-Chloro-6-iodophenol Error. Objects cannot be created from editing field codes. <n="81"/>To a solution of 2-iodophenol (5.0 g) in toluene (200 niL) was added diisopropylamine (32 muL) and sulfuryl chloride (3.07 g) dropwise at 7O0C. After the addition, the mixture was stirred for another hour at 7O0C, before it was quenched with 1 N HCl solution. The organic layer was separated, the aqueous layer was extracted with dichloromethane (3 x 50 mL), and dried over Na2SO4. The product was purified by silica gel flash chromatography eluting with 20% ethyl acetate in heptane to give 2-chloro-6- iodophenol(4.84 g) as an off-white solid. 1H NMR (300 MHz, CDC13/TMS) delta 7.60 (dd, J = 8.1, 1.2 Hz, IH), 7.30 (dd, J = 8.1, 1.5 Hz, IH), 6.62 (dd, J= 8.1, 7.8 Hz, IH), 5.96 (br, IH); 13C NMR (75 MHz, CDCI3/TMS) delta 151.01, 137.94, 129.85, 123.03, 119.44, 83.81. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With triethylamine; magnesium chloride; In acetonitrile; at 10 - 72℃; for 2h; | 4-(nitrooxy)butyl (2R)-7-benzyl-6-chloro-2-(trifluoromethyl)-2H-chromene-3- carboxylate; Step 1; Preparation of 2-hydroxy-4-iodobenzaldehyde; [0168] To a chilled solution of commercially available 2-iodophenol (30 g, 136 mmole) in ACN was added MgCl2 (19.5 g, 204 mmole) portion-wise while maintaining the temperature below 10 0C, followed by paraformaldehyde (28.6 g, 954 mmole) and TEA (76 mL, 545 mmole) producing a 15 C exotherm. The solution was heated to 72 0C for 2 h. The reaction was cooled to room temperature and poured into Saturated aqueous Ammonium Chloride (500 mL), extracted with ethyl acetate (2 X 150 mL). The combined organic phases were washed with aqueous NaHCO3 solution (2 X 150 mL), aqueous IN HCl solution (2 X 150 mL), and brine (2 X 150 mL), dried over Na2SO4, filtered and concentrated in vacuo. The crude material was subjected to flash chromatography (Silica, 5% Ethyl acetate/ Hexane). Desired fractions were collected and combined, removed solvent in vacuo producing the ethyl ester (27 g, 79%) as a yellow solid. This salicylaldehyde was of suitable purity to use without further purification. |
79% | With triethylamine; magnesium chloride; In acetonitrile; at 10 - 72℃; for 2h; | [0232] To a chilled solution of commercially available 2-iodophenol (30 g, 136 mmole) in ACN was added MgCl2 (19.5 g, 204 mmole) portion-wise while maintaining the temperature below 10 C, followed by PARAFORMALDEHYDE (28.6 g, 954 mmole) and TEA (76 mL, 545 mmole) producing a 15 C exotherm. The solution was heated to 72 C for 2 h. The reaction was cooled to room temperature and poured into Saturated aqueous Ammonium Chloride (500 mL), extracted with ethyl acetate (2 X 150 mL). The combined organic phases were washed with aqueous NAHC03 solution (2 X 150 mL), aqueous 1N HCL solution (2 X 150 mL), and brine (2 X 150 mL), dried OVER NA2S04, filtered and concentrated in vacuo. The crude material was subjected to flash chromatography (Silica, 5% Ethyl ACETATE/HEXANE). Desired fractions were collected and combined, removed solvent in vacuo producing the ethyl ester (27 g, 79%) as a yellow solid. This salicylaldehyde was of suitable purity to use without FURTHER PURIFICATION. HNMR (DMSO-D6/400 MHz) 10.95 (s, 1H), 10.19 (s, 1H), 7.33 (m, 3H), 4.31 (m, 1H). |
79% | With triethylamine; magnesium chloride; In acetonitrile; at 10 - 72℃; for 2h; | EXAMPLE 14; (2R)-6-chIoro-5-(3,3-dimethylbutyl)-2-(trifluoromethyl)-l,7b- dihydrocyclopropa[c]chromene-la(2H)-carboxylic acid; Step 1. Preparation of 2-hydroxy-4-iodobenzaldehyde.; [0185] To a chilled solution of commercially available 2-iodophenol (30 g, 136 mmole) in ACN was added MgCl2 (19.5 g, 204 mmole) portion-wise while maintaining the temperature below 10 0C, followed by paraformaldehyde (28.6 g, 954 mmole) and TEA (76 niL, 545 mmole) producing a 15 C exotherm. The solution was heated to 72 0C for 2 h. The reaction was cooled to room temperature and poured into Saturated aqueous Ammonium Chloride (500 mL), extracted with ethyl acetate (2 X 150 niL). The combined organic phases were washed with aqueous NaHCO3 solution (2 X 150 mL), aqueous IN HCl solution (2 X 150 mL), and brine (2 X 150 mL), dried over Na2SO4, filtered and concentrated in vacuo. The crude material was subjected to flash chromatography (Silica, 5% Ethyl acetate/ Hexane). Desired fractions were collected and combined, removed solvent in vacuo producing the ethyl ester (27 g, 79%) as a yellow solid. This salicylaldehyde was of suitable purity to use without further purification. 1HNMR (DMSO-J6/400 MHz) 10.95 (s, IH), 10.19 (s, IH), 7.33 (m, 3H), 4.31 (m, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With pyridine; dmap; at 20℃; for 72h; | General procedure: Typically to a stirred solution of the arylsulfonyl chloride (2.7 mmol) and 4-DMAP (28mg, 0.23 mmol) in pyridine (20 mL) at room temperature was added 2-iodophenol (0.50g, 2.3 mmol), and the reaction mixture stirred for 3 days at room temperature. The reaction mixture was concentrated, dissolved in toluene (ca. 10 mL) and the resulting solution evaporated in vacuo to azeotropically remove the pyridine. The residue was partitioned between CH2Cl2 and water, the organic layer separated, and the aqueous phase re-extracted twice with more CH2Cl2. The combined organic extract was washed with brine, dried over MgSO4 and evaporated in vacuo. Purification of the residue by column chromatography on silica gel furnished the corresponding sulfonate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With N-Methyldicyclohexylamine; t-BuXPhos palladacycle Gen 2; In toluene; at 100℃; for 1h;Inert atmosphere; | General procedure: To a flask were added 1-phenylprop-2-en-1-ol (5) (1.196 mL, 9.09 mmol), 2-iodophenol (6) (1 g, 4.55 mmol) and tBuXPhos Pd G2 precatalyst (0.156 g, 0.227 mmol). Then toluene (18 mL) was added to the flask and the solvent was degassed by bubbling N2 through the solution for 15 min. Cy2NMe (2.420 mL, 11.36 mmol) was then added to the flask and the solvent was degassed by bubbling N2 through the solution for an additional 5 min. The reaction mixture was heated to 100 C for 1 h, cooled to r.t. and concentrated to 1/3 volume. The residue was purified by silica gel chromatography to give 0.91 g (88%) of compound 7 as a colorless oil. The spectroscopic data obtained for this compound are in accordance with the previously prepared material.7 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 135℃; for 12h;Inert atmosphere; | In a nitrogen atmosphere, add 2.6-difluoro-p-bromoiodobenzene (0.32 g, 1.01 mmol),o-iodophenol (0.88g, 4.00mmol) and potassium carbonate (0.552mg, 4.00mmol),Then 15 mL of NMP (N-methylpyrrolidone) was added, and the reaction was carried out at 135 C for 12 hours;After the reaction was completed, it was filtered and washed three times with petroleum ether. The organic solutions were combined and concentrated;The crude product was purified with a silica gel column, the eluent was petroleum ether, and the final product was 0.31 g of a white solid with a yield of 43%; |