Structure of 13526-66-4
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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. : | 13526-66-4 |
Formula : | C6H3BrClN3 |
M.W : | 232.47 |
SMILES Code : | ClC1=NN2C(C=C1)=NC=C2Br |
MDL No. : | MFCD09027274 |
InChI Key : | PFHPKMPWBFJZEY-UHFFFAOYSA-N |
Pubchem ID : | 12872323 |
GHS Pictogram: |
![]() |
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 | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.7 |
TPSA ? Topological Polar Surface Area: Calculated from |
30.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.93 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.31 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.15 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.03 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.34 |
Solubility | 0.106 mg/ml ; 0.000455 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.58 |
Solubility | 0.608 mg/ml ; 0.00262 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.19 |
Solubility | 0.15 mg/ml ; 0.000647 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 |
-6.08 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) |
2.28 |
* 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 |
---|---|---|
93% | In tert-butyl alcohol; at 155.0℃; for 3.0h; | 3-Bromo-6-chloroimidazo[1,2-b]pyridazine (50.0 mg, 0.215 mmol), morpholine (70.0 mg, 0.803 mmol) and t-butyl alcohol (0.5 mL) were heated at 155 C. for 3 hours. Water (2.0 mL) was then added to the reaction mixture. After 15 minutes of additional stirring, tan solids were filtered and washed with water. Evaporation under high vacuum gave 3-bromo-6-morpholin-4-yl-imidazo[1,2-b]pyridazine as tan solids (47 mg, 75%).MS (ESI (+)m/z): 282.56 (M+H+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of sodium hydroxide (3.0 g, 75 mmol) in water (100 mL) was added <strong>[1364890-61-8](R)-2-(3-fluorophenyl)pyrrolidine hydrochloride</strong> (15.7 g, 68 mmol). This was stirred for 20 minutes and then extracted with EtOAc (3×100 mL). The EtOAc fractions were combined, dried over anhydrous sodium sulfate, filtered and reduced to dryness to yield (R)-2-(3-fluorophenyl)pyrrolidine (I-14A) as a light yellow oil. To this oil was added spray dried potassium fluoride (40 g, 680 mmol), 3-bromo-6-chloroimidazo[1,2-b]pyridazine (I-2) (15.7 g, 68 mmol) and DMSO (80 mL). The resulting heterogeneous mixture was then stirred at 100 C. for 72 hours. The reaction mixture was then poured into stirring water (500 mL) and stirred at room temperature for 30 minutes. This mixture was extracted with EtOAc (4×200 mL). The combined organic layers were washed with brine (4×100 mL), dried over anhydrous sodium sulfate, filtered and reduced to dryness to yield a yellow oil. The crude product was then purified using flash chromatography on silica with hexanes/EtOAc gradient to yield (R)-3-bromo-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (X-1). 1H NMR (400 MHz, MeOD-d4) delta 7.48 (d, J=9.6 Hz, 1H), 7.33 (s, 1H), 7.24 (m, 1H), 6.99 (d, J=7.6 Hz, 1H), 6.92 (d, J=10 Hz, 1H), 6.86 (dt, J=8.8, 2.8 Hz, 1H), 6.60 (d, J=10 Hz, 1H), 5.03 (dd, J=10, 3.2 Hz, 1H), 3.88-3.82 (m, 1H), 3.65 (q, J=7.6 Hz, 1H), 2.46-2.36 (m, 1H), 2.03-1.95 (m, 2H), 1.91-1.85 (m, 1 H). MS m/z 361.1 (M+1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
250 mg | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In water; acetonitrile; at 140℃; for 1.08333h;Microwave irradiation; | A mixture of 3-bromo-6-chloro-imidazo[1,2-b]pyridazine (1.0 g, 4.3 mmol), (4-(((tert- butoxycarbonyl)amino)methyl)phenyl)boronic acid (1.08 g, 4.3 mmol), K2C03 (1.48 g, 10.7 mmol) and dichlorobis(triphenylphosphine)palladium(ll) (150 mg, 0.21 mmol) in MeCN/water(16 ml/4 ml) was heated in a microwave at 140C for 35mm Additional (4-(((tert-butoxycarbonyl)amino)-methyl)phenyl)boronic acid (0.54 ) and dichlorobis(triphenylphosphine)-palladium(ll) (50 mg) was added and again heated in microwave at 140C for 30 mm. The reaction mixture was filtered and MeCN was removed. The water layer was diluted with water and extracted with DCM. The combined DCM was dried over MgSO4 and concentrated. The residue was subjected ISCO (0-80% EtOAc inhexane) to give the titled compound (250 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; at 100℃; for 21h;Inert atmosphere; | General procedure: To a solution under N2 of3-bromo-6-chloro-imidazo[1,2-b]pyridazine (1 g, 4.3 mmol) in dioxane (45 mL), Pd[P(C6H5)3]4(0.248 g, 0.2 mmol), 5-indole-5-boronic acid (0.728 g, 4.51 mmol) and Na2CO3(2 M, 7.7 mL) were added. The mixture was stirred for 21 h at 100 C. Thereaction was monitored by TLC. The solvent was evaporated under reducedpressure. The crude residue was diluted and stirred in AcOEt and ammoniumchloride solution (saturated). The product was extracted with AcOEt, and theorganic layer was washed with NaCl solution. The organic layer was dried overNa2SO4, filtered, and evaporated under reduced pressure.The crude residue was purified by chromatography on silica gel using DCM-AcOEt(6:4) afforded 6a in 72% yield(0.840 g) as a light green powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere; | General procedure: In a 25 mL round-bottom flask containing dioxane/H2O (V:V= 5:1) (3 mL), Na2CO3(95.1 mg, 0.688 mmol), 3-bromo-6-chloro-imidazo[1,2-b]pyridazine (80mg, 0.344 mmol), substituted boronicacid (0.361 mmol) and Pd(PPh3)4(11.9 mg, 0.01 mmol) were added andreacted at 80 C under N2. Whenthe reaction was complete (TLC control), the organic solvent was removed. The crude material was then purified by silica gel columnchromatography to give desired products 4a-n, which were characterized by M. p., 1HNMR, 13CNMR and HR-MS. |
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