Structure of 123664-84-6
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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. : | 123664-84-6 |
Formula : | C14H15NO4S |
M.W : | 293.34 |
SMILES Code : | CS(=O)(NC1=CC(OC)=CC=C1OC2=CC=CC=C2)=O |
MDL No. : | MFCD13152085 |
Boiling Point : | No data available |
InChI Key : | HKQJXMJGWKDFTA-UHFFFAOYSA-N |
Pubchem ID : | 10803650 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 20 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 77.72 |
TPSA ? Topological Polar Surface Area: Calculated from |
73.01 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.92 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.74 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.75 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.58 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.57 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.31 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.5 |
Solubility | 0.093 mg/ml ; 0.000317 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.93 |
Solubility | 0.0346 mg/ml ; 0.000118 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.14 |
Solubility | 0.00213 mg/ml ; 0.00000726 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) |
Yes |
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) |
Yes |
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 |
0.0 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) |
2.85 |
* 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 |
---|---|---|
157.6 g | With hydrogenchloride; aluminum (III) chloride; water; In nitromethane; at 10 - 20℃; for 16.0h; | Add to a 1000 mL reaction flask300 mL of nitromethane,Adding 203 g of anhydrous aluminum trichloride in portions, After cooling to room temperature, add 114g aminoacetonitrile hydrochloride; to a temperature below 20 C, 150 g of intermediate III (<strong>[123664-84-6]4-phenoxy-3-methanesulfonamidoanisole</strong>) was added; after stirring for 10 minutes, a dry hydrogen chloride gas was introduced, Ventilation for about 15h, the end of the reaction. The reaction solution was slowly added to 1200 g of 2 mol / L dilute hydrochloric acid at a controlled temperature of 10 C or less, for stirring 1h, filter, solid with a small amount of water (about 80mL) washing, drying; and then 150mL ethyl acetate beating, filter dry,Dry; then the solid and then twice the volume of 95% (volume percentage) of ethanol reflux lh cooling, filtration, solid bake to moisture qualified,157.6 g of the final product (alpha-amino-2-methoxy-4-methanesulfonamido-5-phenoxyacetophenone hydrochloride), 105.07% by weight, and a purity of 99.49% For 168.8 to 17.1.4 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.9% | With hydrogenchloride; In pyridine; water; ethyl acetate; | (4) 10.0 g of 3-amino-4-phenoxyanisole was dissolved in 50 ml of pyridine. Thereto was dropwise added 5.59 g of methanesulfonyl chloride in 10 minutes with ice-cooling. The mixture was stirred for 1 hour at 20-25 C. The reaction mixture was introduced into a mixture of 200 ml of ethyl acetate and 100 ml of water. The resulting organic layer was separated and washed with three 100-ml portions of 2N hydrochloric acid and then with a saturated aqueous sodium chloride solution. The organic layer was separated, dried with anhydrous magnesium sulfate, and subjected to distillation under reduced pressure to remove the solvent. The resulting crystal was recrystallized from isopropyl alcohol to obtain 12.5 g (yield: 91.9%) of 3-methylsulfonylamino4-phenoxyanisole having a melting point of 109.5-111 C. IR (KBr) cm-1: 3250, 1610, 1585, 1480, 1320, 1220, 1150 NMR (CDCl3)delta: 2.94 (3H, s), 3.81 (3H, s), 6.36-7.43 (9H, m) |
276.47 g | With pyridine; at 5 - 30℃; for 1.5h;Green chemistry; | (1) 169 g of 4-methoxy-2 nitrophenol was dissolved in a mixture of 1500 ml of 70% ethanol and 40 ml of 4N HCl, the reaction liquid was heated to 75 C; Then, 196 g of iron powder was uniformly added to the reaction liquid in three batches in 20 minutes. The reaction was stirred rapidly and controlled to no starting material. After completion of the reaction, a saturated solution of sodium carbonate was added to adjust pH = 9 to obtain 2-amino-4-methoxyphenol. (2) 84 g of powdered potassium hydroxide prepared in (1) was added to 2-amino-4-methoxyphenol, stirred, and heated at 160 C for 3.5 hours, and the reaction was completed to obtain a dry salt; 1.89 g of copper powder and 188.4 g of bromobenzene were sequentially added thereto, and stirred at 180 C, mix to discoloration, heat to 200 C, and heat for 2 hours. After cooling, 1200 ml of water and 300 ml of diethyl ether were poured and distilled to give 3-amino-4-phenoxy-anisole. (3) The 3-amino-4-phenoxy-anisole prepared in (2) was dissolved in 800 ml of anhydrous pyridine, the solution was cooled to 5 C, and 137.5 g of methylsulfonyl chloride was added dropwise. After completion of the dropwise addition, the reaction was stirred at room temperature at 30 C, and a developing solvent (EA:PE volume ratio of 1:3) was added thereto, and the raw material was controlled until no raw material, and the reaction time was 1.5 h. After the reaction was completed, the reaction solution was poured into water and extracted with ethyl acetate. Twice, combining organic phases; Wash with 2N HCl until the aqueous layer is pH <7, then washed twice with water, dried over anhydrous magnesium sulfate, and then evaporated to ethyl ether. (5-methoxy-2-phenoxy - benzenesulfonamide quality 276.47g, a purity of 99.658%, 93.93% yield). |
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