Structure of 864076-05-1
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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. : | 864076-05-1 |
Formula : | C6H7BrN2O2 |
M.W : | 219.04 |
SMILES Code : | O=C(C1=NC(Br)=CN1C)OC |
MDL No. : | MFCD13189816 |
InChI Key : | ROEZBNMDDJUDSC-UHFFFAOYSA-N |
Pubchem ID : | 53302209 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 42.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.12 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.22 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.97 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.36 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.87 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.17 |
Solubility | 1.48 mg/ml ; 0.00675 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.74 |
Solubility | 3.95 mg/ml ; 0.018 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.73 |
Solubility | 4.05 mg/ml ; 0.0185 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 |
-6.77 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) |
2.22 |
* 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 |
---|---|---|
15.6% | Step 2To a stirred solution of 2,2,2-trichloro-l-(l-methyl-lH-imidazol-2-yl)ethanone (12.42 g, 54.6 mmol) in THF (40 mL) at -10 0C was added n-bromosuccinimide (6.95 ml, 81.9 mmol). The reaction mixturewas kept at -10 0C for 2 h, warmed to RT with stirring for 12 h and concentrated. The residue was purified with ISCO using straight DCM. The solid obtained was dissolved in MeOH (40 mL), 60percent NaH (80 mg) was added and the reaction mixture heated to 75 0C for 1 h. The reaction mixturewas concentrated and the residue purified with ISCO using 0-10percent EtOAc in DCM to give methyl 4-bromo-l-methyl-lH-imidazole-2- carboxylate (1.86 g, 15.6percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With ammonia; In methanol; at 20℃; for 16h; | To the saturated solution of ammonia in MeOH was added 165 mg of <strong>[864076-05-1]4-bromo-1-methyl-1H-imidazole-2-carboxylic acid methyl ester</strong> and the resulting mixture was stirred at 20° C. for 16 h. The solution was evaporated to give 4-bromo-1-methyl-1H-imidazole-2-carboxylic acid amide (154 mg, yield 100percent). LC-MS calcd for C5H6BrN3O (m/e) 202.97, obsd 204 and 206 [M+1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | A suspension of 1-(4-bromo-l-methyl-1H-imidazol-2-yl)-2,2,2-trichloroethanone (0.266 g, 868 muiotaetaomicron, Eq: 1) in methanol (1.11 g, 1.41 ml, 34.7 mmol, Eq: 40) was heated to reflux for 3 hours then at room temperature overnight. To the reaction mixture, sodium methoxide (15.6 mg, 16.1 mu, 86.8 muiotaetaomicron, Eq: 0.1) was added and stirring was continued at room temperature for 3 hours. The reaction mixture was concentrated in vacuo. The residue was purified by chromatography on silica gel to afford the desired product as a light brown solid (155 mg, 81 percent). MS (m/z) = 219.1, 221.1 [(M+H)+]. | |
68% | In methanol; at 25℃; for 0.333333h; | To the solution of 1.18 g of 1-(-4-bromo-1-methyl-1H-imidazol-2-yl)-2,2,2-trichloroethanone in 10 mL of methanol was added 42 mg of sodium methoxide and the resulting mixture was stirred at 25° C. for 20 min. TLC showed completion of the reaction. The solution was evaporated, redissolved in 30 mL of DCM, washed with water (15 mL.x.2) and brine (15 mL). The solution was dried over anhydrous sodium sulfate and filtered. The residue was purified by silica gel column (DCM/MeOH=60/1) to give 4-bromo-1-methyl-1H-imidazole-2-carboxylic acid methyl ester (0.575 g, yield 68percent). 1H NMR (300 MHz, CDCl3) delta 7.02 (s, 1H), 4.00 (s, 3H). 3.93 (s, 3H). LC-MS calcd for C6H7BrN2O2 (m/e) 217.97, obsd 219 and 221 [M+1]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42.7% | With bis-triphenylphosphine-palladium(II) chloride; cesium fluoride; In ethanol; water; at 100℃; for 0.75h;Microwave irradiation; | A solution of (3^)-3-hydroxy-l-methyl-3-[2-[3-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)phenyl]ethynyl]pyrrolidin-2-one (73 mg., 0.21 mmol), methyl 4-bromo-l- methyl-lh-imidazole-2-carboxylate (40 mg, 0.18 mmol), cesium fluoride (54 mg, 0.36 mmol) and bis(triphenylphosphine)palladium(II) dichloride (12.5 mg, 0.018 mmol) in ethanol (1.5 mL) and water (1.0 mL) was degassed. The reaction mixture was heated in microwave at 100 °C for 45 min. The reaction was filtered through celite. The crude product was purified by flash chromatography (MeOH/DCM) then submitted for rHPLC to give product (27 mg, 42.7percent). LC-MS (ES, m/z): 354 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dmap; at 20℃; for 0.5h; | A solution of SI-2 (1.91 g, 6.24 mmol) and DMAP (305 mg, 2.50 mmol) in MeOH (31 mL) was stirred for 30min at room temperature. The reaction mixture was evaporated and the obtained residue was purified by silica gel column chromatography (SiO2, EtOAc) to give the desired product 6a (1.32 g, 96percent yield) as white solid. |
96% | With dmap; at 25℃; for 0.5h; | A solution of the compound 2-4 (1.91 g, 6.24 mmol) and DMAP (305 mg, 2.50 mmol) in MeOH (31 mL) was stirred at room temperature for 30 minutes. The reaction mixed liquid was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (SiO2, EtOAc), so as to provide the target compound 2-5 (1.32 g, 96percent yield) as a white solid substance. Melting point (Mp.) 94-95° C.; 1H NMR (400 MHz, CDCl3) delta 3.94 (s, 3H), 4.01 (s, 3H), 7.03 (s, 1H); 13C NMR (100 MHz, CDCl3) delta 36.0, 52.4, 115.6, 125.7, 135.9, 158.6; IR (ATR) nu 1713, 1446, 1243, 1122, 953 cm?1; HRMS ((+)-ESI-TOF) m/z: [M+H]+ Calcd. for C6H8BrN2O2+ 218.9764; Found 218.9749. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a suspension of methylamine hydrochloride (78.6 mg, 1.16 mmol, Eq: 3) in dioxane (3.88 ml) was added dropwise 2 M trimethylaluminum in toluene (582 mu, 1.16 mmol, Eq: 3) (slight gas evolution) and the mixture was stirred for 30 minutes at room temperature. Then methyl 4- bromo-1 -methyl-1H-imidazole-2-carboxylate (0.085 g, 388 muiotaetaomicron, Eq: 1) was added and the mixture was heated to reflux overnight. The reaction mixture was quenched with 120 ul of water (strong gas evolution) and the mixture was stirred for 15 minutes at room temperature. Then sodium sulfate was added and the stirring was continued for 1 hour. The suspension was filtered and washed with dichloromethane and dichloromethane/methanol 9: 1. The obtained solution was concentrated in vacuo. The residue was purified by chromatography on silica gel to afford the desired product as a white solid (51 mg, 60 percent). MS (m/z) = 218.1, 220.1 [(M+H)+]. |
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