Structure of 644982-55-8
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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. : | 644982-55-8 |
Formula : | C8H4BrNO |
M.W : | 210.03 |
SMILES Code : | N#CC1=CC(C=O)=CC(Br)=C1 |
MDL No. : | MFCD09261040 |
InChI Key : | FKGQJUAOTNPVFD-UHFFFAOYSA-N |
Pubchem ID : | 53425523 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-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 | 0.0 |
Molar Refractivity | 44.24 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.86 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.52 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.57 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.51 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.1 |
Solubility | 0.167 mg/ml ; 0.000796 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.08 |
Solubility | 0.176 mg/ml ; 0.000839 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.29 |
Solubility | 0.107 mg/ml ; 0.000512 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) |
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 |
-5.76 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 |
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) |
1.82 |
* 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 pyridine; copper(l) cyanide; In DMF (N,N-dimethyl-formamide); at 140℃; | A mixture of 3, [5-DIBROMOBENZALDEHYDE] (1 [G),] copper cyanide (0.331 [G)] and pyridine (0.3 mL) in DMF (30 mL) was heated to [140C] overnight. The solution was allowed to cool to r. t. and dropped into water (30 [ML),] then exctracted with Et20 (15 mL). The organic phase was dried, concentrated in vacuo and the residue was purified by flash chromatography (CH, [CH/ACOET FROM] 95: 5 to 80: 20) to give the title compound (64 mg) as a yellow oil. T. I. c.: CH/AcOEt [8] : 2, Rf=0.52 (detection with 2, [4-DINITROPHENYLHYDRAZINE).] NMR [(CDCI3)] : [6] (ppm) 10.0 (s, [1H)] ; 8.20 (s, [1H)] ; 8.10 (s, [1H)] ; 8.00 (s, [1H).] [IR (NUJOL, CM~1)] : 2235.70 [(C--N)] ; 1700.14 [(C=O).] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of methylamine (2M in MeOH-1. 5 mL) was dropped into a solution of intermediate 82 (0.640 g) in anhydrous MeOH (3 mL) under a Nitrogen atmosphere. The mixture was stirred at r. [T.] for 2 hours, then after cooling at 0 [C,] potassium borohydride (0.160 mg) was added stepwise. The solvent was removed in vacuo, the residue diluted with water (5 mL) and extracted with AcOEt (2 x 5 mL). The organic phase was dried, concentrated in vacuo and the residue was purified by SCX cartridge (load with MeOH and elution with [NH3] 0.25M in MeOH) to give the title compound (48 mg) as a yellow oil. T. [I.] c.: DCM/MeOH 8: 2, Rf=0.61 (detection with ninhydrine). MS (ES/+): [M/Z=225] [M+H] +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 160℃; for 0.333333h;Microwave irradiation; | Example 41 : 5-(3-cyano-5-{f(2,2,2-trif luoroethyl)amino1methyl)phenv?-3-ri- (ethylsulfonyl)-4-piperidinvn-1H-indole-7-carboxamide trifluoroacetate; To a solution of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)-1H-indole-7-carboxamide (46 mg, 0.1 mmol) in dioxane (2.0 mL, 0.7 mL) was added <strong>[644982-55-8]3-bromo-5-formylbenzonitrile</strong> (68 mg, 0.3 mmol) and K2CO3 (83 mg, 0.6 mmol) in a microwave tube. The reaction mixture was degassed for 5 min before addition of tetrakis (triphenylphosphosphine) palladium (0) (11 mg, 0.01 mmol). The reaction was heated in a microwave for 20 min at 160s C. It was then purified by Gilson Preparatory EPO <DP n="114"/>HPLC to give 5-(3-cyano-5-formylphenyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1 H-indole-7- carboxamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In 1,4-dioxane; | Example 41 5-(3-cyano-5-[(2,2,2-trifluoroethyl)amino]methyl}phenyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide trifluoroacetate To a solution of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carboxamide (46 mg, 0.1 mmol) in dioxane (2.0 mL, 0.7 mL) was added <strong>[644982-55-8]3-bromo-5-formylbenzonitrile</strong> (68 mg, 0.3 mmol) and K2CO3 (83 mg, 0.6 mmol) in a microwave tube. The reaction mixture was degassed for 5 min before addition of tetrakis (triphenylphosphosphine) palladium (0) (11 mg, 0.01 mmol). The reaction was heated in a microwave for 20 min at 160 C. It was then purified by Gilson Preparatory HPLC to give 5-(3-cyano-5-formylphenyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | palladium dichloride; In water; ethyl acetate; acetonitrile; | To a solution of 3-bromo-5-formylbenzamide (1.5 g, 6.58 mmol) in H2O (50.0 mL) and MeCN (50.0 mL) was added PdCl2 (117 mg, 0.658 mmol). The mixture was stirred for 72 h at room temperature and another portion of H2O (100 mL) and MeCN (100 mL) was added followed with addition of PdCl2 (100 mg, 0.56 mol). The mixture was stirred for another 12 hr and concentrated. The residue was dissolved in EtOAc (200 mL), washed with brine (3*50.0 mL), dried over Na2SO4 and concentrated, and then was purified by chromatography (10% EtOAc in hexanes) to give 550 mg of 3-bromo-5-formylbenzonitrile (40%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With toluene-4-sulfonic acid; In benzene; for 4h;Reflux; | 3-Bromo-5-[1 ,3]dioxolan-2-yl-benzonitrle(6); 3-Bromo-5-formyibenzonitriie(3g, 14 28mmol), ethylene glycol(1 61ml,28 deltadeltammoi), p-toluenesulfonic acid monohydrate(136mg, 0 71mmo.), and benzene(80ml) were placed in a 250ml round bottom fiask equipped with a Dean-Stark trap and a reflux condenser The mixture was then heated to reflux for 4hr After cooling to room temperature, the mixture was diluted with ether, washed with sat NaHCO3 solution, d?ed with MgSO4, filtered, and concentrated in vacuo to afford 3 6g(100%) of the title compound as a pale yeliow oil The product was used directly to the next reaction1H-NMR(200MHz, CDCI3) delta 4 03-4 11 (4H, m), 5 79(1 H, s), 7 71 (1 H1 s), 7 77(1 H, s), 7 84(1 H1 S) m/z (El) 254 (IvI+) |