Structure of 891785-28-7
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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. : | 891785-28-7 |
Formula : | C9H7BrN2 |
M.W : | 223.07 |
SMILES Code : | NC1=CC2=C(C=CC(Br)=C2)C=N1 |
MDL No. : | MFCD11101002 |
InChI Key : | PQKLBIXLXFRNKT-UHFFFAOYSA-N |
Pubchem ID : | 45789831 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 53.85 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.83 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.59 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.04 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.4 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.38 |
Solubility | 0.0923 mg/ml ; 0.000414 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.91 |
Solubility | 0.274 mg/ml ; 0.00123 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.2 |
Solubility | 0.014 mg/ml ; 0.000063 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 |
-5.92 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) |
1.64 |
* 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 |
---|---|---|
69.7% | Step 1 To a mixture of <strong>[614731-04-3]1-tert-butoxycarbonyl-4-fluoro-piperidine-4-carboxylic acid</strong> (XXXVIII) (1.07 mL, 13.99 mmol), HATU (7.09 g, 18.65 mmol) and DIPEA (4.87 mL, 27.97 mmol) in DMF (40 mL) was stirred for 10 min. Then, 6-bromoisoquinolin-3-amine (XII) (2.08 g, 9.32 mmol) and DMAP (0.23 g, 1.86 mmol) was added then the mixture was heated to 80 C. overnight. The reaction mixture was concentrated, the residue partitioned between EtOAc/sat.NaHCO3, organic layer separated, washed with water and brine. The organics were then separated and dried (MgSO4) before concentration to dryness. The crude was then purified by flash column chromatography (0?40% EtOAc/hexanes). The desired fractions were concentrated to dryness en vacuo and recrystallized with hexanes to obtain tert-butyl 4-[(6-bromo-3-isoquinolyl)carbamoyl]-4-fluoro-piperidine-1-carboxylate (XXXIX) (2.94 g, 6.50 mmol, 69.7% yield) as a white solid. ESIMS found for C20H23BrFN3O3 m/z 452.1 (79BrM+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68.3% | A mixture of <strong>[68947-43-3]1-methylpiperidine-4-carboxylic acid</strong> (LVIII) (1.07 mL, 16.14 mmol), HATU (7.67 g, 20.17 mmol) and DIPEA (8.2 mL, 47.07 mmol) in MeCN (50 mL) was stirred for 10 min. 6-bromoisoquinolin-3-amine (XV) (3.0 g, 13.45 mmol) and DMAP (0.33 g, 2.69 mmol) was then added and the mixture was heated to 80 C. overnight. The solvent was evaporated and the residue purified via column chromatography (80 g of silica gel) (CHCl3?3% MeOH/7 N NH3 in CHCl3) to afford N-(6-bromoisoquinolin-3-yl)-1-methylpiperidine-4-carboxamide (LIX) as a beige solid (3.2 g, 9.19 mmol, 68.3% yield). ESIMS found for C16H18BrN3O m/z 347.90 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.3% | To a mixture of 6-bromoisoquinolin-3-amine (XV) (4.52 g, 20.27 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (LIV) (5.62 g, 22.12 mmol), KOAc (5.43 g, 55.29 mmol), and Pd(dppf)Cl2 (3.0 g, 3.69 mmol) in dioxane (10 mL) was purged with nitrogen and then heated at 90 C. for 2 h. The reaction was cooled to room temperature before adding the <strong>[54044-79-0]2-bromo-5-methyl-1,3,4-thiadiazole</strong> (LV) (3.30 g, 18.43 mmol), K2CO3 (7.64 g, 55.29 mmol) and Pd(dppf)Cl2 (3.0 g, 3.69 mmol). The mixture was heated at 90 C. for another 4 h. The solvent was removed under high vacuum and the residue was purified by column chromatography (0?100% EtOAc/hexanes) to produce 6-(5-methyl-1,3,4-thiadiazol-2-yl)isoquinolin-3-amine (LVI) as a yellow solid (4.30 g, 17.75 mmol, 96.3% yield). ESIMS found for C12H10N4S m/z 243.0 (M+1). |
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