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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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Structure of 452-77-7
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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. : | 452-77-7 |
Formula : | C7H8FN |
M.W : | 125.14 |
SMILES Code : | NC1=CC=C(C)C(F)=C1 |
MDL No. : | MFCD00007762 |
InChI Key : | MGRHBBRSAFPBIN-UHFFFAOYSA-N |
Pubchem ID : | 9957 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H300-H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P301+P310-P305+P351+P338 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 35.77 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.56 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.92 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.14 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.24 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.01 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.78 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.69 |
Solubility | 2.56 mg/ml ; 0.0205 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.05 |
Solubility | 11.1 mg/ml ; 0.0887 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.66 |
Solubility | 0.273 mg/ml ; 0.00218 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) |
No |
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 |
-6.41 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 |
2.0 |
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) |
1.0 |
* 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 |
---|---|---|
44.8% | at 0 - 80℃; for 6 h; | Preparation of 3-fluoro-4-methylphenol: 3-Fluoro-4-methylaniline (5g, 39.95 lmmol) was dissolved in 10percent sulfuric acid aqueous solution (100ml). Thereafter, the temperature was lowered to O°C. thereto sodium nitrate (5.5g, 79.902mmol) was added, and the reaction mixture was stirred at same temperature for 30 minutes. Then the reaction mixture was stirred at 500C for 30 minutes, and the last time, stirred at 8O°C for 5 hours. Ice water was added to quench the reaction, and aqueous layer was extracted with ethyl acetate. Combined organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (n-hexane:ethyl acetate = 8:1) to give 2.26g (yield: 44.8percent, colorless oil) of the target compound.1H NMR(400MHz, CDCl3): 6.98(t, J=8.6Hz, IH), 6.52(m, 2H), 5.82(br, IH),2.12(s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With bromine; potassium carbonate In dichloromethane at -15℃; for 1 h; | Example 28; Preparation of Intermediate Compound 28G; 28G; Step A - Synthesis of Compound 9B; 28A 28B; A mixture of compound 28A (6.00 g, 47.9 mmol) and anhydrous potassium carbonate (6.70 g, 48.5 mmol) in anhydrous dichloromethane (130 mL) was cooled to -15 0C in a salt-ice bath and then added dropwise to a solution of bromine (7.70 g, 48.2 mmol) in anhydrous dichloromethane (80 mL). After addition was complete, the reaction was allowed to stir at -15 0C for 1 hour. Ice water (100 mL) was added to the reaction mixture and the aqueous layer was extracted with dichloromethane (2 x 100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to provide compound 28B (11.0 g, quant.), which was used without further purification. |
100% | With bromine; potassium carbonate In dichloromethane at -15℃; for 1 h; | Example 9; Preparation of Intermediate Compound 9G; 9G; Step A - Synthesis of Compound 9B; A mixture of compound 9A (6.00 g, 47.9 mmol) and anhydrous potassium carbonate (6.70 g, 48.5 mmol) in anhydrous dichloromethane (130 mL) was cooled to -15 0C in a salt-ice bath and then added dropwise to a solution of bromine (7.70 g, 48.2 mmol) in anhydrous dichloromethane (80 mL). After addition was complete, the reaction was allowed to stir at -15 0C for 1 hour. Ice water (100 mL) was added to the reaction mixture and the aqueous layer was extracted with dichloromethane (2 x 100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to provide compound 9B (11.0 g, quant.), which was used without further purification. |
100% | With bromine; potassium carbonate In dichloromethane at -15℃; for 1 h; | Example 28; Preparation of Intermediate Compound 28G <n="200"/>; 28G; Step A - Synthesis of Compound 28B; 28A 28B; A mixture of compound 28 A (6.00 g, 47.9 mmol) and anhydrous potassium carbonate (6.70 g, 48.5 mmol) in anhydrous dichloromethane (130 mL) was cooled to -15 0C in a salt-ice bath and then added dropwise to a solution of bromine (7.70 g, 48.2 mmol) in anhydrous dichloromethane (80 mL). After addition was complete, the reaction was allowed to stir at -15 0C for 1 hour. Ice water (100 mL) was added to the reaction mixture and the aqueous layer was extracted with dichloromethane (2 x 100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to provide compound 28B (11.0 g, quant.), which was used without further purification. |
100% | With bromine In dichloromethane at -15℃; for 1 h; Cooling with salt-ice | A mixture of compound SA (6,00 g, 47.9 mrnol) and anhydrous potassium carbonate (6.70 g, 48.5 mmoi) in anhydrous dichloromethane (130 mL) was cooled to -15 0C in a salt-ice bath and then added dropwise to a solution of bromine (7.70 g, 48.2 mmol) in anhydrous dichloromethane (80 mL). After addition was complete, the reaction was allowed to stir at -15 0C for 1 hour. Ice water (100 mL) was added to the reaction mixture and the aqueous layer was extracted with dichloromethane (2 x 100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to provide compound SB (1 1.0 g. quant. ). which was used without further purification. |
100% | With bromine; potassium carbonate In dichloromethane at -15℃; for 1 h; | Example 9; Preparation of Intermediate Compound AA7; Step A - Synthesis of Compound AA2; A mixture of compound AAl (6.00 g, 47.9 mmol) and anhydrous potassium carbonate (6.70 g, 48.5 mmol) in anhydrous dichloromethane (130 mL) was cooled to -15 0C in a salt-ice bath and then added dropwise to a solution of bromine (7.70 g, 48.2 mmol) in anhydrous dichloromethane (80 mL). After addition was complete, the reaction was allowed to stir at -15 0C for 1 hour. Ice water (100 mL) was added to the reaction mixture and the aqueous layer was extracted with dichloromethane (2 x 100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to provide compound AA2 (11.0 g, quant.), which was used without further purification. |
100% | With bromine; potassium carbonate In dichloromethane at -15℃; for 1 h; | Example 19; Preparation of Intermediate Compound AA7; Step A - Synthesis of Compound AA2; A mixture of compound AAl (6.00 g, 47.9 mmol) and anhydrous potassium carbonate (6.70 g, 48.5 mmol) in anhydrous dichloromethane (130 mL) was cooled to -15 0C in a salt-ice bath and then added dropwise to a solution of bromine (7.70 g, 48.2 mmol) in anhydrous dichloromethane (80 mL). After addition was complete, the reaction was allowed to stir at -15 0C for 1 hour. Ice water (100 mL) was added to the reaction mixture and the aqueous layer was extracted with dichloromethane (2 x 100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to provide compound AA2 (11.0 g, quant.), which was used without further purification. |
100% | With bromine; potassium carbonate In dichloromethane at -15℃; | A mixture of compound AA1 (6.00 g, 47.9 mmol) and anhydrous potassium carbonate (6.70 g, 48.5 mmol) in anhydrous dichloromethane (130 mL) was cooled to -15° C. in a salt-ice bath and then added dropwise to a solution of bromine (7.70 g, 48.2 mmol) in anhydrous dichloromethane (80 mL). After addition was complete, the reaction was allowed to stir at -15° C. for 1 hour. Ice water (100 mL) was added to the reaction mixture and the aqueous layer was extracted with dichloromethane (2.x.100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to provide compound AA2 (11.0 g, quant.), which was used without further purification. |
33% | With bromine; potassium carbonate In dichloromethane at -15℃; for 1 h; | To a suspension of 3-fluoro-4-methylaniline (6.0 g, 48mmol) and K2C03 (6.6 g, 48 mmol) in DCM (80 mL) at -15 °C was added Br2 (2.4 mL, 48mmol) in DCM (20 mL) slowly. The reaction mixture was stirred at -15 °C for 1 h. Themixture was then quenched with ice water (30 mL), diluted with water (80 mL), andextracted with DCM (3 x 50 mL), dried and concentrated. The residue was purified via silica gel chromatography (0 - 10 percent EtOAc in petroleum ether) to give the title compound (3.2 g, 33percent) as a white solid. MS (ES+) C7H7BrFN requires: 203, found: 204 [M+Hf’ |
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