Structure of 5228-61-5
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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.
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CAS No. : | 5228-61-5 |
Formula : | C6H5BrN2O2 |
M.W : | 217.02 |
SMILES Code : | NC1=CC(Br)=CC=C1[N+]([O-])=O |
MDL No. : | MFCD09056836 |
InChI Key : | RMIFLIVHJLREFJ-UHFFFAOYSA-N |
Pubchem ID : | 5314766 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 47.37 |
TPSA ? Topological Polar Surface Area: Calculated from |
71.84 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.42 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.9 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.95 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.05 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.33 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.2 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.72 |
Solubility | 0.413 mg/ml ; 0.0019 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.03 |
Solubility | 0.202 mg/ml ; 0.00093 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.28 |
Solubility | 1.14 mg/ml ; 0.00527 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) |
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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.27 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 |
3.0 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) |
2.19 |
* 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 |
---|---|---|
63% | Step 1: 3-Amino-4-nitrobenzonitrile (274) [0431] A suspension of bromoarene 2 (801mg; 3.7 MMOL) and zinc cyanide (570mg; 4. 85MMOL ; 1. 3eq. ) in degassed DIMETHYLFORMAMIDE (15 mL) was stirred at room temperature under nitrogen in the dark for 45 min and then treated with tetrakis (TRIPHENYLPHOSPHINE) PALLADIUM (O) (310mg, 1. 6MMOL). The mixture was stirred at 90C for 18h; filtered through a celite pad, concentrated under reduced pressure and purified by flash chromatography on silica gel, eluent EtOAc-hexane (1 : 1) to afford the title compound 274 (380 mg, 63% YIELD). H NMR: (400.2 MHz, CDCI3) 8 (ppm): 8.22 (d, J=8.6 Hz; 1H); 7.19 (d, J=1.8 Hz; 1H) ; 6.95 (dd, J=1.8, 8.6 Hz; 1H) ; 6.27 (bs; 2H). MS: CALC : 163.1 ; found: 164.1 (M+H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | To a solution of SM-1 (1.08 g, 5.0 mmol), TEA (3.03 g, 30.0 mmol) in DCM (20 mL) was added triphosgene (1.49 g, 5.0 mmol) under ice bath. The solution was warmed to room temperature and stirred for 1 h. TEA (2.02 g, 20.0 mmol) and SM-0 (965 mg, 5.0 mmol) was then added. The resulting solution was heated at 50 °C for 1 h. After cooling to room temperature, the solution was diluted with DCM. The resultant was washed with brine, dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (DCM : MeOH = 100 : 1~ 30 : 1) to give 130-1 (900 mg, 50 percent) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 1h;Inert atmosphere; Microwave irradiation; | To a stirred solution of 5-bromo-2-nitroaniline (CAS Number 5228-61-5; 0.700 g, 3.23 mmol) and <strong>[376584-63-3]1H-pyrazol-5-ylboronic acid</strong> (CAS Number 376584-63-3; 0.720 g, 6.45 mmol) in DMF:water (2:1; 9 ml) was added Na2CO3 (1.03 g, 9.68 mmol) at rt. The reaction mixture was degassed withnitrogen for 20 mm and PdC12(dppf) (0.166 g, 0.23 mmol) was added. The mixture was heated at130°C for lh under microwave irradiation. The reaction mixture was cooled to rt, poured into water(40 ml) and was extracted with EtOAc (2 x 40 ml). Combined organic extracts were dried overanhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue waspurified by flash column chromatography (60percent EtOAc in hexane) to give 2-nitro-5-(1H-pyrazol-5-yl)aniline (0.69 g, Quantitative). LCMS: Method C, 1.568 mi MS: ES+ 205.38. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h; | Dissolve raw material 2 (i.e. 5-bromo-2-nitroaniline) (4.34g, 20mmol) in 50mLTo N,N-dimethylformamide, potassium carbonate (5.53g, 40mmol) was added in sequence,Methyl iodide (2.84g, 20mmol), react at room temperature for 12 hours,Intermediate 3(3.74g, 81% yield). |
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