Structure of 288246-16-2
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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. : | 288246-16-2 |
Formula : | C4H2BrN3 |
M.W : | 171.98 |
SMILES Code : | N#CC1=C(Br)C=NN1 |
MDL No. : | MFCD00105683 |
InChI Key : | ZXVFKQRZKKGVNJ-UHFFFAOYSA-N |
Pubchem ID : | 2735623 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 31.0 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.47 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.72 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.96 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.04 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.17 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.7 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.85 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.97 |
Solubility | 1.83 mg/ml ; 0.0106 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.65 |
Solubility | 3.86 mg/ml ; 0.0224 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.17 |
Solubility | 1.17 mg/ml ; 0.00678 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 |
-6.67 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 |
0.0 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) |
1.8 |
* 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 |
---|---|---|
40% | Step 1 4-Bromo-2-(tetrahydro-pyran-2-yl) -2H-pyrazole-3-carboniotatriotaleBr /N NV-O / /[00412] 4-Bromo-lH-pyrazole-3-carbomt?le (150mg, 0 87mmol) is dissolved in 3,4-dihydro-2H-pyran (25 mL, 2 6mmol) in the presence of a catalytic amount of TFA (lmg, 0 009mmol) The reaction mixture is stirred at 950C for 1 hour, cooled and then quenched using NaH (1 2mg, 0 052mmol) After removing the solvent, the residue is pu?fied by silica gel column chromatography elutmg with a mixture of 3 1 petroleum ether-dichloromethane, followed by 10 1 petroleum ether-ethyl acetate The fractions containing the desired compounds are collected and concentrated in vacuo to afford the title compound as a colorless oil (90mg, 40%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2.0h; | Example 3; 4-(4-Bromo-3-cyanopyrazole-1-yl)benzoic acid ethyl ester; A suspension of <strong>[288246-16-2]4-bromo-1H-pyrazole-3-carbonitrile</strong> (0.52 g), 4-fluoro-benzoic acid ethyl ester (0.56 g) and cesium carbonate (1.5 g) in N,N-dimethylformamide (10 mL) was stirred at 100C for 2 hours. After cooling to ambient temperature, this reaction mixture was poured into water, and this mixture was extracted with ethyl acetate. This organic layer was washed with brine, dried over anhydrous magnesium sulfate. The organic layer was through an aminopropyl silica gel, and this filtrate was concentrated under reduced pressure. This obtained residue was washed with a mixed solvent of n-hexane/diethyl ether = 5/1 to give the title compound (0.25 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | With pyridine; copper diacetate; at 20℃; for 72.0h;Molecular sieve; | To a solution of 4-bromo-3-cyano-lH-pyrazole 49 (172 mg, 1 mmol) in pyridine (3 mL) was added 2,5-difluorophenyl boronic acid (237 mg, 1.5 mmol), and 4A molecular sieves. The mixture was stirred for 72 h at room temperature. The reaction was worked-up with saturated NaHC0 and EtOAc extraction. The organic layer was separated and aqueous was extracted with EtOAc. The combined organic phase was dried over a2S04, filtered, and concentrated to give crude product. The crude product was purified on ISCO columns. Fractions containing pure product were combined and evaporated to give 50 (70 mg, 25%) as a blue wax. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; at 20 - 100℃;Inert atmosphere; | At room temperature, compound (36c) (1.63 g, 4.36 mmol), <strong>[288246-16-2]4-bromo-1H-pyrazole-3-carbonitrile</strong> (36d) (500 mg,2.91 mmol), a potassium carbonate (1.00 g, 7.28 mmol) solution (10 mL) and 1,4-dioxane (50 mL) were sequentiallyadded to a 150 mL reaction flask, and nitrogen atmosphere protection was applied. After the reaction solution was stirreduntil homogenous, Pd(dppf)Cl2 (213 mg, 0.29 mmol) was added under protection of nitrogen. The system was heatedto 100C, and the reaction was allowed to proceed overnight. After thin layer chromatography indicated the reactionwas complete, the reaction solution was quenched with water, extracted with ethyl acetate, dried over anhydrous sodiumsulfate, concentrated under reduced pressure, and purified by column chromatography on silica gel, to afford compound(36e) (255 mg, white solid), yield: 26%. MS (ESI, m/z): 340 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46 mg | With potassium carbonate; potassium iodide; In acetonitrile; at 50℃; for 48.0h; | was prepared: to a solution of Bis-CFhCI PF1022a in acetonitrile (4.8 ml_, 0.02M) was 4-bromo-1 H-pyrazole-3-carbonitrile added (66 mg, 0.38 mmol), potassium bicarbonate (38 mg, 0.38 mmol) and potassium iodide (95 mg, 0.57 mmol). The mixture was heated to 50C for 48 hours. After cooling to room temperature, the solvent was removed under reduced pressure and the residue partitioned between water and DCM. The organics were separated, dried over MgS04 and evaporated. The crude material was purified by reverse phase HPLC to give the title product as a white solid (46 mg). |
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