Structure of 5417-17-4
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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. : | 5417-17-4 |
Formula : | C9H9ClO3 |
M.W : | 200.62 |
SMILES Code : | O=CC1=CC=C(OC)C(OC)=C1Cl |
MDL No. : | MFCD00084942 |
InChI Key : | SAWHDJTZESXNMM-UHFFFAOYSA-N |
Pubchem ID : | 79445 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.82 |
TPSA ? Topological Polar Surface Area: Calculated from |
35.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.08 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.95 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.17 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.4 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.05 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.46 |
Solubility | 0.702 mg/ml ; 0.0035 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.32 |
Solubility | 0.958 mg/ml ; 0.00478 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.22 |
Solubility | 0.12 mg/ml ; 0.0006 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 |
-6.14 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 |
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) |
1.73 |
* 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 |
---|---|---|
96% | With sodium chlorite; aminosulfonic acid; In 1,4-dioxane; water; at 0℃; for 0.5h;Inert atmosphere; | To a solution of 4 (20.06g, 100mmol) in 1,4-dioxane (300mL) were added a solution of sulfamic acid (21.36g, 220mmol) in water (200mL) and NaClO2 (19.9g, 220mmol) in water (100mL) at 0°C. After stirring for 30minat 0°C, the mixture was quenched by a solution of sodium bisulfite (45.8g, 440mmol) in water (200mL). The aqueous layer was extracted with EtOAc and the combined extracts were washed with water and brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to afford 5 (20.74g, 96percent). 1H NMR (DMSO?d6) delta: 13.04 (br s, 1H), 7.63 (d, J=8.9Hz, 1H), 7.11 (d, J=8.9Hz, 1H), 3.89 (s, 3H), 3.74 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48.1% | With boron tribromide; In dichloromethane; at 0 - 25℃; for 4h; | <strong>[5417-17-4]2-chloroveratraldehyde</strong> (3 g, 15.0 mmol) wasdissolved in DCM (30 mL). BBr3 (4.61 mL, 48mmol) was added dropwise at 0°C. After addition,the reaction mixture was warmed to room temperature and stirred for 4 h. The reaction mixture wasextracted with EA and the organic phase was washed with water and brine, dried over anhydrousNa2SO4, filtered and then the filtrate was concentrated in vacuo. The residue was purified bychromatography on silica gel with DCM/MeOH (50:1) to give 73a-2 (1.24 g, 48.1percent) as a whitesolid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tetrahydroborate; In ethanol; at 20℃; | <strong>[5417-17-4]2-Chloro-3,4-dimethoxybenzaldehyde</strong> (2.5 g, 12.4 mmol) was dissolved in ethanol (50 ml), sodium borohydride (930 mg, 25 mmol) was added, and the mixture was stirred overnight at room temperature. A treatment according to a conventional method using ethyl acetate as an extraction solvent gave a crude product. The obtained crude product was dissolved in thionyl chloride (5 ml) and, after stirring at room temperature for 4 hr, treated according to a conventional method using ethyl acetate as an extraction solvent. The obtained crude product was dissolved in dimethyl sulfoxide (30 ml), sodium cyanide (610 mg, 12.4 mmol) was added, and the mixture was stirred overnight at room temperature. A treatment according to a conventional method using ethyl acetate as an extraction solvent gave a crude product, which was successively purified by silica gel column chromatography to give a nitrile intermediate (830 mg, 3.93 mmol) | |
With sodium tetrahydroborate; In dichloromethane; at 20℃; for 0.5h; | General procedure: To a solution of various benzaldehydes 4aew (10 mmol) dissolved in methanol (50 mL) was added sodium borohydride (20 mmol) at room temperature, and the mixturewas stirred at the same temperature for 30 min and concentrated under reduced pressure. The residue was diluted with methylene chloride (500 mL) and washed with water, and dried over anhydrous Na2SO4, and concentrated under reduced pressure to give the corresponding crude phenylmethanols 5a-w |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With chlorine; In N,N-dimethyl-formamide; | Step 1. Preparation of 2-chloro-3-hydroxy-4-methoxybenzaldehyde Chlorine gas is introduced into a solution of 3-hydroxy-4-methoxybenzaldehyde in N,N-dimethylformamide at -10° to -30° C. When the addition of chlorine is complete, the reaction mixture is stirred at -25° C. for 30 minutes and, then, poured into water. The product is separated by filtration and washed with water. The wet product may be dried or used directly in the next step. Average yield, 73percent. Step 2. Preparation of 2-chloro-3,4-dimethoxybenzaldehyde (1) | |
With chlorine; potassium carbonate; dimethyl sulfate; In N-methyl-acetamide; chloroform; water; | EXAMPLE 2 Isovanillin (200 g, 1.32 mole) was suspended in 1200 cc chloroform. Chlorine (103 g, 1.45 mole) was added by means of 3 500 cc portions of carbon tetrachloride, in which it was dissolved. The suspension was stirred vigorously during the addition and the reaction was kept around 25° by a water bath. The suspension was stirred for 22 minutes after the completion of the addition of chlorine. The precipitate was filtered and crystallized from methanol, then recrystallized from isopropanol/ethyl acetate. Yield 98.7 g (40percent, m.p. 204°-206°) of 2-chloro-3-hydroxy-4-methoxybenzaldehyde. The aldehyde product (189.3 g, 1.02 mole) was suspended in 1 l. of dry dimethylformamide, 350 g of potassium carbonate was added. 145 cc (124 g, 1.54 mole) of dimethyl sulfate was added dropwise over a 20 minute period. After the addition the reaction was heated on the steam bath for 5 minutes. 70 cc of water were added and the reaction was again heated for 5 minutes on the steam bath. The mixture was then poured into ice water and the precipitate was collected. It was crystallized from acetic acid/water (800 cc-50 cc). A second crop was obtained from the mother liquor. Yield 180 g (90percent) of 2-chloro-3,4-dimethoxybenzaldehyde after drying, m.p. 69°-70°. | |
With chlorine; potassium carbonate; dimethyl sulfate; In N-methyl-acetamide; chloroform; water; | EXAMPLE 1 Isovanillin (200 g, 1.32 mole) was suspended in 1200 cc chloroform. Chlorine (103 g, 1.45 mole) was added by means of 3 500 cc portions of carbon tetrachloride, in which it was dissolved. The suspension was stirred vigorously during the addition and the reaction was kept around 25° by a water bath. The suspension was stirred for 22 minutes after the completion of the addition of chlorine. The precipitate was filtered and crystallized from methanol, then recrystallized from isopropanol/ethyl acetate. Yield 98.7 g (40percent, m.p. 204-206°) of 2-chloro-3-hydroxy-4-methoxybenzaldehyde. The aldehyde product (189.3 g, 1.02 mole) was suspended in 1 l. of dry dimethylformamide, 350 g of potassium carbonate was added. 145 cc (124 g, 1.54 mole) of dimethyl sulfate was added dropwise over a 20 minute period. After the addition the reaction was heated on the steam bath for 5 minutes. 70 cc of water were added and the reaction was again heated for 5 minutes on the steam bath. The mixture was then poured into ice water and the precipitate was collected. It was crystallized from acetic acid/water (800 cc-50 cc). A second crop was obtained from the mother liquor. Yield 180 g (90percent) of 2-chloro-3,4-dimethoxybenzaldehyde after drying, m.p. 69°-70°. |
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