Structure of 89891-65-6
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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. : | 89891-65-6 |
Formula : | C8H4BrClN2 |
M.W : | 243.49 |
SMILES Code : | BrC1=CC=C2C(=C1)N=C(C=N2)Cl |
MDL No. : | MFCD02955309 |
InChI Key : | AZUMKBQKUXTHCM-UHFFFAOYSA-N |
Pubchem ID : | 4913253 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 52.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
25.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.36 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.92 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.17 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.75 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.81 |
Solubility | 0.0381 mg/ml ; 0.000156 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.12 |
Solubility | 0.184 mg/ml ; 0.000754 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.8 |
Solubility | 0.00384 mg/ml ; 0.0000158 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-5.71 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) |
1.96 |
* 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 |
---|---|---|
54.2% | With ammonia; In 1,4-dioxane; at 70.0℃; for 5.0h; | a) 7-bromoquinoxaline-2-amine 7-bromo-2-chloroquinoxaline (1.0 g, 4.13 mmol) and ammonia (7 mL) were added to 1,4-dioxane (7 mL). After reaction under agitation at 70 C for 5 h, the reaction mixture was cooled to rt. Water (10 mL) was added, and EA (30 mL*2) was used for extraction. The organic phases were combined, washed with a saturated saline solution (50 mL), dried with anhydrous sodium sulfate, filtered, and concentrated at reduced pressure to obtain a crude compound. Isolation and purification by column chromatography (silica gel, PE: EA = 3:1 as an eluant) were performed to obtain the targeted compound (500 mg, 54.2% yield, yellow solid). LC-MS (ESI): m/z (M+1) 223.99. |
With ammonium hydroxide; In 1,4-dioxane; at 110.0℃;Sealed tube; | A solution of intermediate 431 ( 1 00 mg, 0.41 mmol) in dioxane (4 niL) and Nu.Eta2Omicron(10 mL, 25%) was stirred in a sealed tube at 1 10C overnight. The mixture was concentrated to give the crude intermediate 432 (108 mg) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | With potassium phosphate; chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); In tetrahydrofuran; water; at 20℃; for 16h;Inert atmosphere; Sealed tube; | XPhos second generation precatalyst (40.5 mg, 0.051 mmol) was added to a thick- walled, screw top tube containing an argon-degassed solution of 7-bromo-2- chloroquinoxaline (250 mg, 1.027 mmol), tert-butyl 3-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-5,6-dihydropyridine-l(2H)-carboxylate (317 mg, 1.027 mmol) and potassium phosphate (545 mg, 2.57 mmol) in THF (5 mL) and water (1 mL). The tube was sealed, and the mixture was stirred at rt for 16 h before it was diluted with ethyl acetate and water. The aqueous layer was separated and the organic layer was extracted twice more with ethyl acetate. The combined organic extract was washed with brine, dried over MgS04, filtered and concentrated to give a light caramel-colored residue. The residue was taken up in a small amount of dichloromethane and charged to a RediSepRf normal phase silica gel Teledyne ISCO 40 g disposable column which was first eluted with hexanes for 120 mL, followed by 0 - 50percent B for 1400 mL where solvent B = ethyl acetate and solvent A = hexanes. After concentration of the eluant, there was isolated the desired product, tert-butyl 3-(7-bromoquinoxalin-2-yl)-5,6-dihydropyridine-l(2H)- carboxylate (56.0 mg, 14percent yield) as a light yellow solid. LCMS: tR (retention time) = 1.51 min; LCMS (ESI) m/z calcd for C18H21BrN302: 390.08, found: 389.95 and 391.95 [M+H]+. LCMS conditions: Injection Vol = 3 uL; Gradient = 2 - 98percent B; Gradient Time = 1.5 min; Flow Rate = 0.8 ml/min; Wavelength = 220 nm; Mobile Phase A = 0: 100 acetonitrile: water with 0.05percent trifiuoroacetic acid; Mobile Phase B = 100:0 acetonitrile:water with 0.05percent trifiuoroacetic acid; Column = Waters Aquity BEH CI 8, 2.1 x 50 mm, 1.7 U (= muiotaeta); Oven Temp = 40 °C. NMR (500MHz, CDCh) delta 9.10 (s, 1H), 8.25 (br. s., 1H), 7.94 (d, J=8.8 Hz, 1H), 7.80 (dd, J=8.8, 2.0 Hz, 1H), 7.04 (br. s., 1H), 4.59 (br. s., 2H), 3.66 (t, J=5.7 Hz, 2H), 2.50 (br. s., 2H), 1.55 (s, 9H). |
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