Structure of 957187-27-8
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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. : | 957187-27-8 |
Formula : | C7H4BrClN2 |
M.W : | 231.48 |
SMILES Code : | ClC1=CN2C(C(Br)=C1)=NC=C2 |
MDL No. : | MFCD12828062 |
InChI Key : | LMPPBTNPACXNDI-UHFFFAOYSA-N |
Pubchem ID : | 26370038 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.9 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.14 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.08 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.75 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.06 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.26 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.46 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.82 |
Solubility | 0.035 mg/ml ; 0.000151 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.11 |
Solubility | 0.179 mg/ml ; 0.000775 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.56 |
Solubility | 0.0636 mg/ml ; 0.000275 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 |
-5.53 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) |
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 |
---|---|---|
89% | In ethanol; water; at 50.0℃; | A mixture of 3-bromo-5-chloropyridin-2-amine (10 g, 49 mmol) and chloroacetaldehyde (50% in H2O, 12 mL, 98 mmol) in ethanol (100 mL) was heated at 50 C. overnight. It was then cooled to room temperature and concentrated. Acetone (30 mL) was added to the residue and the resulting mixture was stirred rapidly for 2 h. The resulting solid was collected through filtration and dried to afford 101a as a yellow solid (10.0 g, 89%). MS: [M+H]+231. 1H NMR (500 MHz, DMSO) delta 9.20 (s, 1H), 8.33 (s, 1H), 8.29 (s, 1H), 8.09 (s, 1H) |
55.2% | In ethanol; for 3.0h;Reflux; | Example 39 2'-amino-6-(6-chloroimidazo[ 1 ,2-a]pyridin-8-yl)- 1 ',2,2-trimethylspiro[chroman-4,4'- imidazol]-5'(l'H)-oneStep A: 3-Bromo-5-chloro-2-pyridinamine (487 mg, 2.35 mmol) was diluted with ethanol (4 mL), followed by the addition of 2-chloroacetaldehyde (614 , 4.69 mmol). The reaction was heated at reflux for 3 hours. The reaction was cooled and loaded onto silica gel eluting with 10-50% ethyl acetate/hexanes to yield 8-bromo-6-chloroimidazo[l,2-a]pyridine (300 mg, 1.30 mmol, 55.2% yield).Step B: 2'-Amino-r,2,2-trimethyl-6-(4,4,5,5-tetramethyl |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 85.0℃; for 12.0h;Sealed tube; | Step B: 2'-Amino-r,2,2-trimethyl-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)spiro[chroman-4,4'- imidazol]-5'(l'H)-one (50 mg, 0.13 mmol; see Example 103, Step A) and 8-bromo-6-chloroimidazo[l,2- ajpyridine (60 mg, 0.26 mmol) were diluted with dioxane (1 mL), followed by the addition of Pd(PPh3)4 (7.5 mg, 0.0065 mmol) and Na2C03 (324 mu, 0.65 mmol). The reaction was sealed, heated to 85C and stirred for 12 hours. The reaction was loaded directly onto silica gel and eluted with 1-10% methanol/DCM (1% Nu¾OmicronEta) to afford 2'-amino-6-(6-chloroimidazo[l,2-a]pyridin-8-yl)-l',2,2- trimethylspiro[chroman-4,4'-imidazol]-5'(rH)-one (18 mg, 0.044 mmol, 34% yield), m/z (APCI-pos) M+l = 410.2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100.0℃; | A 50-mL round-bottomed flask equipped with a reflux condenser was charged with <strong>[957187-27-8]8-bromo-6-chloroimidazo[1,2-a]pyridine</strong> 101a (264 mg, 1.14 mmol), 5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-amine (328 mg, 1.14 mmol), Pd2(dba)3 (102 mg, 0.11 mmol), Xantphos (63 mg, 0.11 mmol), Cs2CO3 (3.58 g, 11.0 mmol), dioxane (20 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100 C. overnight. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:50 methanol/dichloromethane to afford 121a as an orange solid (290 mg, 66%). MS-ESI: [M+H]+385.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100.0℃; for 12.0h;Inert atmosphere; | A mixture of 101a (2.3 g, 10 mmol), 5-(4-methylpiperazin-1-yl)pyridin-2-amine (1.9 g, 10 mmol), XantPhos (576 mg, 1.0 mmol), Pd2(dba)3 (915 mg, 1.0 mmol) and Cs2CO3 (6.5 g, 20 mmol) in dioxane (50 mL) was heated at 100 C. for 12 h under nitrogen. It was then filtered and evaporated in vacuo. The residue was purified by silica-gel column eluting with 1:1 ethyl acetate/petroleum ether to afford 101b as a green solid (1.5 g, 44%). MS: (M+H)+343. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100.0℃; for 5.0h;Inert atmosphere; | A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (60 mL), tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (1.5 g, 5.39 mmol), <strong>[957187-27-8]8-bromo-6-chloroimidazo[1,2-a]pyridine</strong> 101a (3.7 g, 16.18 mmol), and cesium carbonate (3.52 g, 10.79 mmol). XantPhos (312 mg, 0.539 mmol) and Pd2(dba)3 (494 mg, 0.539 mmol) were added, and the reaction mixture was heated at 100 C. for 5 h under nitrogen. After this time the reaction was cooled to room temperature. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified on flash column eluting with 100:1 CH2Cl2/MeOH to afford 102a (1.8 g, 78%). MS: [M+H]+429. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.01 g | With 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); N-ethyl-N,N-diisopropylamine; In toluene; at 100.0℃; for 2.0h;Inert atmosphere; | b) 8-(benzylthio)-6-chloroimidazo[1,2-a]pyridine A mixture of <strong>[957187-27-8]8-bromo-6-chloroimidazo[1,2-a]pyridine</strong> (2.50 g), benzylmercaptan (1.40 mL), tris(dibenzylideneacetone)dipalladium(0) (248 mg), 1,1'-bis(diphenylphosphino)ferrocene (298 mg), DIPEA (3.8 mL) and toluene (20 mL) was stirred under a nitrogen atmosphere at 100 C. for 2 hr. The reaction mixture was filtered to remove an insoluble material and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (3.01 g). 1H NMR (300 MHz, DMSO-d6) delta 4.47 (2H, s), 7.13 (1H, d, J=1.8 Hz), 7.22-7.39 (3H, m), 7.39-7.47 (2H, m), 7.59 (1H, d, J=1.1 Hz), 7.93 (1H, d, J=1.2 Hz), 8.64 (1H, d, J=1.9 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.71 g | With toluene-4-sulfonic acid; In ethanol; at 80.0℃; | A mixture of 3-bromo-5-chloro-2-pyridinamine (5.0 g), bromoacetoaldehyde diethyl acetal (7.3 mL), p-toluenesulfonic acid monohydrate (498 mg) and ethanol (20 mL) was stirred at 80 C. overnight. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give a residue. The obtained residue was washed with ethyl acetate/IPE to give the title compound (4.71 g). (1141) 1H NMR (300 MHz, DMSO-d6) delta 7.68 (1H, d, J=1.2 Hz), 7.75 (1H, d, J=1.8 Hz), 8.06 (1H, d, J=1.2 Hz), 8.91 (1H, d, J=1.8 Hz). |
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