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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+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Structure of 1150271-74-1
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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. : | 1150271-74-1 |
Formula : | C13H17BBrFO2 |
M.W : | 314.99 |
SMILES Code : | CC1(C)C(C)(C)OB(C2=CC=C(CBr)C(F)=C2)O1 |
MDL No. : | MFCD11855987 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P301+P330+P331-P303+P361+P353-P363-P304+P340-P310-P321-P260-P264-P280-P305+P351+P338-P405-P501 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅲ |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.54 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 75.71 |
TPSA ? Topological Polar Surface Area: Calculated from |
18.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.57 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.29 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.8 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.29 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.59 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.16 |
Solubility | 0.022 mg/ml ; 0.0000697 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.64 |
Solubility | 0.0716 mg/ml ; 0.000227 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.51 |
Solubility | 0.000964 mg/ml ; 0.00000306 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) |
Yes |
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) |
Yes |
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 |
-5.69 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 |
2.0 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) |
3.07 |
* 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 potassium carbonate; In N,N-dimethyl-formamide; at 60.0℃; for 3h;Inert atmosphere; | j00634j 2-(4-(Bromomethyl)-3 -fluorophenyl)-4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolane was prepared in three steps from 4-bromo-2-fluoro-1-methylbenzene following the procedure of White, J.R., et al., Tetrahedron Leu. 2010, 51, 3913-3917. In a dry round bottom flask equipped with a stir bar and septum, 2H-benzo[b][1,4]thiazin-3(4H)-one (90 mg, 0.545 mmol), 2-(4-(bromomethyl)-3 -fluorophenyl)-4,4,5,5 -tetramethyl- 1,3,2- dioxaborolane (150 mg, 0.476 mmol), and potassium carbonate (90 mg, 0.652 mmol) were massed. The flask was purged with argon then charged with dry DMF (3 mL). The reaction was stirred at 60 C and monitored by LCMS. After 3 h, reaction was deemed to be complete and cooled to room temperature. The reaction was diluted with ethyl acetate (20 mL), and the organic layer was washed with saturated NaHCO3. The two layers were separated and the aqueous layer was extracted with ethyl acetate (3x20 mL). The organic extracts were combined then washed with saturated LiC1 solution (20 mL) and brine (20 mL). The organic portion was dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash column chromatography on silica gel, eluting with hexanes/ethyl acetate to afford 4-(2-fluoro-4-(4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolan-2- yl)benzyl)-2H-benzo[b][1,4]thiazin-3(4H)-one |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; for 3h; | 2.0 M Methylamine in THF (3 mL, 6 mmol) was added dropwise to a solution of <strong>[1150271-74-1]2-[4-(bromomethyl)-3-fluorophenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (Combi-Blocks, cat No.PN-5656: 200 mg, 0.6 mmol) in THF (10 mL) over 1 hour. After stirring for an additional 2 h, the reaction was concentrated and used without further purification. LC-MS calculated for C14H22BFNO2 (M+H)+: m/z=266.2. found 266.2. | |
In tetrahydrofuran; at 20.0℃; for 2h; | To a solution of 2.0 M methylamine in tetrahydrofuran (3 mL, 6 mmol) was added dropwise a solution of <strong>[1150271-74-1]2-[4-(bromomethyl)-3-fluorophenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (Combi-Blocks, cat PN-5654: 200 mg, 0.6 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred at room temperature for 2 h, then concentrated. The crude product was used in the next step without further purification | |
In tetrahydrofuran; at 20.0℃; for 2h; | Step 1: 1-[2-fluoro-4-(4,4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)phenyl]-N-methylmethanamine To a solution of 2.0 M methylamine in tetrahydrofuran (3 mL, 6 mmol) was added dropwise a solution of <strong>[1150271-74-1]2-[4-(bromomethyl)-3-fluorophenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (Combi-Blocks, catNo.PN-5654: 200 mg, 0.6 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred at room temperature for 2 h, then concentrated. The crude product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Intermediate 264a was prepared in a similar manner as for Intermediate OOld, replacing 2-(4-(bromomethyl)phenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane with 2- (4-(bromomethyl)-3-fluorophenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane. Intermediate 264a was purified by preparative HPLC (method E). LC-MS (Method A5): 0.62 min, [M + H]+ = 328.0; H NMR (400 MHz, MeOH-d4 delta 7.54 - 7.42 (m, 2H), 7.39 (s, IH), 7.30 (t, 7=7.6 Hz, IH), 5.83 (s, 2H), 3.26 (q, 7=7.7 Hz, 2H), 2.72 - 2.66 (m, 6H), 1.41 (t, 7=7.6 Hz, 3H). |
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