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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
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Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Structure of 1214342-44-5
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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.
4.5
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CAS No. : | 1214342-44-5 |
Formula : | C6H3BrClFO2S |
M.W : | 273.51 |
SMILES Code : | FC1=CC(=CC(Br)=C1)S(Cl)(=O)=O |
MDL No. : | MFCD13185364 |
InChI Key : | HZJBQCUMWMMHMK-UHFFFAOYSA-N |
Pubchem ID : | 51000079 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3265 |
Packing Group: | Ⅲ |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
42.52 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.74 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.02 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.7 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.79 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.57 |
Solubility | 0.0743 mg/ml ; 0.000272 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.29 |
Solubility | 0.141 mg/ml ; 0.000516 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.07 |
Solubility | 0.0233 mg/ml ; 0.0000853 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) |
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 |
-6.02 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) |
2.04 |
* 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 |
---|---|---|
76% | With ammonium hydroxide; In 1,4-dioxane; water; at 20℃; | Intermediate S3: 3-bromo-5-fluorobenzene-1-sulfonamide Aqueous 30% NH4OH (17 mL) was added to a solution of <strong>[1214342-44-5]3-bromo-5-fluorobenzene-1-sulfonyl chloride</strong> S2 (0.450 g, 1.65 mmol) in dioxane (14 mL) and the reaction was allowed to proceed overnight at RT. Water was added and the mixture was extracted twice with EtOAc and twice with DCM. The combined organic layers were dried over sodium sulfate and the solvent was evaporated to afford title compound as orange solid (0.320 g, 1.26, 76% yield), which was used without any further purification. MS/ESI- 252.0-254.0 [M-H]-, Rt=0.76 min. (254.1-256.1) (Method A). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | Intermediate S2: 3-bromo-5-fluorobenzene-1-sulfonyl chloride To a solution of 3-bromo-5-fluoroaniline (0.500 g, 2.63 mmol) in glacial acetic acid (0.70 mL) cooled in an ice bath, concentrated hydrochloric acid (2.15 mL) was added. Then, a solution of sodium nitrite (0.199 g, 2.89 mmol) in water (0.45 mL) was slowly added maintaining the temperature around 0 C. After completion of the addition, the reaction mixture was further stirred for 20 min. The resulting solution was slowly added to a freshly prepared mixture of aqueous ?40% sodium bisulfite solution (1.915 mL, 7.36 mmol), copper chloride (0.052 g, 0.526 mmol), glacial acetic acid (5.0 mL) and concentrated hydrochloric acid (1 mL) at room temperature and the reaction was stirred at RT for 2.5 h. The mixture was then cooled to 0 C., additional sodium nitrite (0.5 eq) was added and the stirring was continued at r.t. for 1 h. The mixture was extracted with EtOAc and the organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to afford title compound which was used without any additional purification (0.450 g, 1.65 mmol, 63% yield). 1H NMR (400 MHz, DMSO-d6) delta ppm 7.54-7.58 (m, 1H), 7.50-7.54 (m, 1H), 7.30-7.36 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19.4 g | With triethylamine; In dichloromethane; at 20℃; for 16h; | Step 3: Preparation of 3-bromo-5-fluoro-N-(3-methoxypropyl)benzenesulfonamide To a solution of <strong>[1214342-44-5]3-bromo-5-fluoro-benzenesulfonyl chloride</strong> (23.0 g, 84.12 mmol) in DCM (250 mL) was added 3-methoxypropylamine (8.25 g, 92.53 mmol) and Et3N (25.5 g, 252.3 mmol). The mixture was stirred at rt for 16 hrs, and then partitioned between DCM (200 mL) and water (200 mL). The organic layer was separated, then washed with brine (200 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography to give 3-bromo-5-fluoro-N-(3-methoxypropyl)benzenesulfonamide (19.4 g) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; N-chloro-succinimide; In water; acetonitrile; at 0 - 20℃; for 2h; | Step 2: Preparation of 3-bromo-5-fluoro-benzenesulfonyl chloride To a solution of 1-benzylsulfanyl-3-bromo-5-fluoro-benzene (25.0 g, 84.12 mmol) in MeCN (250 mL) was added 2M HCl (33.6 mL) and NCS (44.9 g, 336.5 mmol) at 0 oC. The reaction mixture was stirred at rt for 2 hrs, and then concentrated in vacuo. The residue was partitioned between DCM (500 mL) and water (100 mL). The organic layer was separated, then washed with brine (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo to give 3- bromo-5-fluoro-benzenesulfonyl chloride (23.0 g, crude), which was used directly in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; at 20℃; | To a stirred solution of 3-bromo-5-fluorobenzene-l-sulfonyl chloride (40 mg, 0.146 mmol) in dichloromethane (471 pl) was added pyrrolidine (30.2 m, 0.366 mmol). The reaction solution was stirred at room temperature overnight. The reaction solution was purified by column chromatography, eluting with a 0-100% EtO Ac/hexanes gradient. This afforded l-((3-bromo-5-fluorophenyl)sulfonyl)pyrrolidine (53.2 mg, 118%) as a white solid. LCMS (ESI, m/z), 308.0, 310.0 [M+H]+. 1H NMR (400 MHz, CDCb) d 1.81-1.89 (m, 4H), 3.27-3.34 (m, 4H), 7.50 (tdd, 7=7.53, 7.53, 2.38, 1.51 Hz, 2H), 7.76-7.83 (m, 1H). |
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