Structure of 27246-81-7
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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. : | 27246-81-7 |
Formula : | C6H8BrClN2 |
M.W : | 223.50 |
SMILES Code : | [H+].C1=C(NN)C=CC=C1Br.[Cl-] |
MDL No. : | MFCD00012933 |
InChI Key : | RPYIPFXHIKXRKS-UHFFFAOYSA-N |
Pubchem ID : | 33757 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 47.2 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.05 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 |
2.65 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.45 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.27 |
Solubility | 0.119 mg/ml ; 0.000533 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.1 |
Solubility | 0.177 mg/ml ; 0.000794 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.94 |
Solubility | 0.255 mg/ml ; 0.00114 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
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 |
-5.78 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 |
0.56 |
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) |
1.73 |
* 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 |
---|---|---|
74% | In acetic acid; for 16h;Heating / reflux; | A solution of 3-BROMOPHENYLHYDRAZINE hydrochloride (0.5 g, 2.2 mmol) and ethyl 5,5- dimethyl-2, 4-DIOXOHEXANOATE (0. 54 g, 2. 68 mmol) in acetic acid (10 ML) was refluxed for 16 hours. The reaction was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated bicarbonate and brine, and dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography (4. 8 : 0.2 HEXANES/ETHYL acetate) to give ethyl 1- (3- BROMOPHENYL)-5-TERT-BUTYL-LH-PYRAZOLE-3-CARBOXYLATE (0.59 g, 74 %) as a syrup. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; PPA; In 5,5-dimethyl-1,3-cyclohexadiene; hexane; dichloromethane; acetone; | PREPARATION 9 4-Bromo-2-methyl-1H-indole and 6-bromo-2-methyl-1H-indole 3-Bromophenylhydrazine hydrochloride (26.5 g) was partitioned between etherand excess 2N sodium hydroxide solution. The ether layer was separated, washed with brine, dried (MgSO4) and evaporated. The residue was redissolved in ether (25 ml) and the solution was cooled in ice. Acetone (25 ml) was added and the mixture was allowed to stand for 20 minutes and then evaporated. The residue was dissolved in acetone (25 ml), the solution was evaporated and the residue azeotroped with xylene. The residue was dissolved in xylene (30 ml) and the solution was added dropwise to stirred polyphosphoric acid (200 g) at 90 C. The mixture was stirred at 100 C. for 4 hours and then cooled and poured into ice water with stirring. The mixture was extracted twice with ether, and the combined extracts were washed with brine and dried (MgSO4). The solvent was evaporated and the residue was chromatographed on silica gel using dichloromethane/hexane (1:4) as eluent. The product fractions were combined and evaporated, and the residue was crystallized twice from hexane to give 6-bromo-2-methyl-1H-indole (8.70 g), m.p. 132-134 C. delta(CDCl3): 2.38(3H,s), 6.15(1H,s), 7.12(1H,dd), 7.32(1H,d), 7.36(1H,d), 7.77(1H,br). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Oxalyl chloride (1.20 mL, 14.2 mmol) was added dropwise to a stirred solution of <strong>[89489-53-2]tetrahydro-2H-thiopyran-4-carboxylic acid</strong> (, 2.00 g, 13.7 mmol) in dichloromethane (25 mL). Then, two drops of N,N'-dimethylformamide were added and stirring was continued. After 1.5 hours, the resultant solution was added dropwise over 30 minutes to a stirred, cooled (ice-bath) solution of (3-bromophenyl)hydrazine hydrochloride (3.05 g, 13.7 mmol) and triethylamine (4.20 mL, 30.1 mmol) in dichloromethane (40 mL). After the addition, the mixture was warmed to room temperature and stirred for two hours. The mixture was then concentrated in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was washed with 4% aqueous sodium hydrogen carbonate solution, dried (MgSO4) and evaporated. The residue was triturated with diethyl ether and the solid was filtered and dried to give the title compound (2.57 g, 60%) as an off-white solid. LRMS (m/z): 315/317 (M+1)+. 1H-NMR δ (DMSO-d6): 1.62-1.76 (m, 2H), 2.00-2.07 (m, 2H), 2.28-2.37 (m, 1 H), 2.63-2.67 (m, 4H), 6.66 (d, J=9.0 Hz, 1 H), 6.79 (t, J=3.0Hz, 1 H), 6.84 (d, J=9.0 Hz, 1H), 7.08 (t, J=9.0 Hz, 1H), 8.00 (brs, 1H), 9.71 (brs, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of the mixture of regioisomers from Step A above (1.1 g, 4.4 mmol) in xylene (20 mL) was added manganese(IV)-oxide (3.80 g, 40 mmol). The mixture was stirred at 110 C (internal temperature) overnight. The solid material (Mn02) was filtered off through a paper filter, and the solvents were removed under reduced pressure. The residue was purified on HP-Sil cartridges, by employing a dichloromethane/methanol gradient (100/0 -> 90/10) to obtain a mixture of regioisomers (0.47 g, 43%) (0148) MS (ESI): m/z = 247.19/249.18 [M+H]+ |
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