Structure of 61655-77-4
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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. : | 61655-77-4 |
Formula : | C9H13ClN4 |
M.W : | 212.68 |
SMILES Code : | CN1CCN(C2=CN=CC(Cl)=N2)CC1 |
MDL No. : | MFCD12024895 |
InChI Key : | ZMVHGTJAFGHEBY-UHFFFAOYSA-N |
Pubchem ID : | 9920770 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H319-H317 |
Precautionary Statements: | P305+P351+P338-P280 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.56 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 63.3 |
TPSA ? Topological Polar Surface Area: Calculated from |
32.26 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.18 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.01 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.12 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.38 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.05 |
Solubility | 1.91 mg/ml ; 0.00899 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.28 |
Solubility | 11.2 mg/ml ; 0.0529 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.44 |
Solubility | 0.765 mg/ml ; 0.0036 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 |
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 |
-6.88 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 |
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) |
2.6 |
* 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 |
---|---|---|
83% | With triethylamine; In ethanol; for 1.25h;Reflux; | General procedure: To a solution of absolute ethanol (5 mL) and dichlorodiazine (3.36 mmol) in a 50mL round-bottom flaskwas added triethylamine (5.03 mmol), followed by the amine (5.03 mmol). The mixture was stirred either under reflux of ethanol (for dichloropyridazine and for dichloropyrazine) or at room temperature (for dichloropyrimidines). The reaction was monitored by GC. Once the starting dichlorodiazinewas completely consumed, the mixture was poured into a saturated NH4Cl solution (20 mL), then extracted with CH2Cl2 (320 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated under vacuum. The crude solid was triturated in petroleum ether, filtered through a Buchner to afford the pure product. |
80% | In dichloromethane; | Example 295-Cyano-furan-2-carboxylic acid [4-methyl-6.-(4-methyl-piperidin- 1 -yl)-3 ,4,5 ,6- tetrahydro-2H- [1,2'] -bipyrazinyl-5 -yl] -amide a) 6'-Chloro-4-methyl-3,4,5,6-tetrahydro-2H-[l,2']bipyrazinyl; To a solution of 2,6-dichloropyrazine (400 mg, 2.68 mmol) in 6 mL of CH2Cl2 was added 4-methylpiperidine (1.2 eq, 3.2 mmol) and allowed to stir overnight. The reaction was diluted with CH2Cl2 (50 mL) washed with H2O (2x50 mL) and dried (K2CO3) to give 450 mg (80%) of the title compound as a white solid. Mass spectrum (ESI, m/z): Calcd. for CnH15ClN2, 211.0 (M+H), found 211.1. |
80% | General procedure: To the N,N-dimethylformamide (DMF) (4 mL) solution of N,N-dimethylethylenediamine (95 mL, 0.87 mmol) was added K2CO3 (0.19 g, 1.3 mmol). After the reaction mixture was stirred at room temperature (RT) for 30 min, 2,6-dichloropyrazine (0.10 g, 0.67 mmol) was added and the resulting reaction mixture was further stirred at RT for 12 h. After removal of solvent in vacuo, the residue was treated with dichoromethane. Insoluble impurities were removed by filtration. Removal of solvent in vacuo gave the product 0.095 g in 71 % yield; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8% | With nitronium tetrafluoborate; In acetonitrile; at -50 - 0℃; for 0.5h; | b) 6'-Chloro-4-methyl-5'-nitro-3,4,5,6-tetrahydro-2H-[l,2']bipyrazinyl; To a solution of 6'-chloro-4-methyl-3,4,5,6-tetrahydro-2H-[l,2']bipyridinyl (450 mg (2.12 mmol, as prepared in the previous step) in 7 mL of CH3CN was added NO2BF4 (198 mg, 1.48 mmol) in three portions. After 10 min, the reaction was cooled to the freezing point of -50 C and another 98 mg (0.73 mmol) Of NO2BF4 was added in one portion. The reaction was stirred for 20 min, warmed to 0 C, and placed in a freezer overnight. At this time the reaction was quenched with satd aq NaHCO3 (50 mL), extracted with EtOAc (2 x 20 mL), and dried (K2CO3). The EtOAc was removed in vacuo and the crude material was purified by preparative thin layer chromatography (20% EtOAc- hexane) to afford 42 mg (8%) of the title compound as a yellow solid.1H-NMR (CDCl3; 400 MHz): delta 7.65 (s, IH), 3.91-3.86 (m, 2H), 3.11-3.04 (m, 2H), 1.66-1.80 (m, 3H), 1.34- 1.24 (m, 2H), 1.01 (d, 3H, J = 6.4 Hz); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100℃; for 12.33h;Inert atmosphere; Sealed tube; | EXAMPLE 87: 5-(6-(4-methylpiperazin-l-yl)pyrazin-2-yl)-lH-pyrrolor2,3-b1pyridineThe starting material 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrrolo[2,3-b]pyridine (124) (50 mg, 0.2 mmol, 1 eq) and 2-chloro-6-(4-methylpiperazin-l-yl)pyrazine (63) (44 mg, 0.2 mmol, 1 eq) in DMF (5 mL) was degassed and purged under argon atmosphere for 10 min. To this reaction mixture was charged Cs2C03 (133 mg, 0.4 mmol, 2 eq) followed by addition of Pd(PPh3)4 (0.01 mg, 0.04 mmol) and degassing and purging under argon for an additional 10 min. The reaction mixture was heated at 100C for 12 h in a sealed tube. After completion of the reaction, the reaction mixture was diluted with CHC13 and filtered through Celite. The solvents were distilled off and the crude material was submitted for flash column purification in neutral alumina using 2% MeOH/CHCl3 to obtain pale yellow solid compound 5-(6-(4- methylpiperazin-l-yl)pyrazin-2-yl)-lH-pyrrolo[2,3-b]pyridine 125 in 20 mg quantity. The compound 125 was confirmed by 1HNMR and LCMS. 1H NMR (400 MHz, CDC13) delta: 8.96 (d, J=1.5Hz 1H), 8.55 (d, J=1.70Hz, 1H), 8.30 (s, 1H), 8.08 (s,lH), 7.35 (m, J=3.04, 1H), 6.60(m, J=1.95 1H), 3.75 (m, J=5.00, 4H), 2.58 (m, J=5.12, 4H), 2.38 (s , 3H); MS m/z 294.9 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 100℃;Inert atmosphere; Sealed tube; | Reaction Scheme 12EXAMPLE 43 : 1 -(4-methoxybenzyl)-3 -methyl-5 -(6-(4-methylpiperazin- 1 -yl)pyrazin-2- yP- 1 H-pyrazolo [3 ,4-b"|pyridineTo a stirred solution of 8 and 63 in 1,4 dioxane and water was added CS2CO3, the solution degassed, purged with nitrogen for 15 min, Pd(PPh3)4 was added and the reaction mass was again purged with nitrogen for another 15 min. The reaction mass was heated at 100C in a sealed tube overnight. After completion of the reaction the reaction mass was partitioned between ethyl acetate and water and the organic layer was separated and again extracted with ethyl acetate. The combined organic layer was dried over sodium sulphate and the solvent completely distilled off to get the crude. The crude was passed through 100-200 mesh silica gel eluting the pure compound at 70-80% ethyl acetate in hexane as off white coloured solid compound 64 (25 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; ethanol; at 120℃; for 0.166667h;Microwave irradiation; | General procedure: A microwave tube filled with compound 2 (0.35 mmol), alkoxy heteroaromatic chloride or amine heteroaromatic chloride (0.38 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.010 mmol), 2 M potassium carbonate (1.7 mmol) in dioxane : ethanol (2 : 3) was heated in the microwave reactor at power 100 W and 120 C for 10 min. After solvent was removed in vacuo, the residue was treated with ethyl acetate and washed with water. The obtained organic layer was dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; ethanol; at 120℃; for 0.166667h;Microwave irradiation; | General procedure: A microwave tube filled with compound 2 (0.35 mmol), alkoxy heteroaromatic chloride or amine heteroaromatic chloride (0.38 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.010 mmol), 2 M potassium carbonate (1.7 mmol) in dioxane : ethanol (2 : 3) was heated in the microwave reactor at power 100 W and 120 C for 10 min. After solvent was removed in vacuo, the residue was treated with ethyl acetate and washed with water. The obtained organic layer was dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel. |