Structure of 7250-67-1
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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. : | 7250-67-1 |
Formula : | C6H13Cl2N |
M.W : | 170.08 |
SMILES Code : | Cl.ClCCN1CCCC1 |
MDL No. : | MFCD00012718 |
InChI Key : | FSNGFFWICFYWQC-UHFFFAOYSA-N |
Pubchem ID : | 81668 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.41 |
TPSA ? Topological Polar Surface Area: Calculated from |
3.24 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.41 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.74 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.83 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.91 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.58 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.28 |
Solubility | 0.891 mg/ml ; 0.00524 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.12 |
Solubility | 1.29 mg/ml ; 0.00758 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.72 |
Solubility | 3.26 mg/ml ; 0.0192 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
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) |
No |
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 |
-5.63 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 |
2.0 |
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 |
1.0 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) |
1.43 |
* 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 |
---|---|---|
Production Example 15-2 6-Iodo-1-(2-pyrrolidin-1-ylethyl)-1H-indazole and 6-iodo-2-(2-pyrrolidin-1-ylethyl)-2H-indazole Potassium carbonate was added to a DMF solution (10 mL) of the compound (1 g) obtained in Production Example 15-1, and stirred at room temperature for 30 minutes. N-(2-chloroethyl)pyrrolidine hydrochloride (1.1 g) was added to the reaction liquid, and stirred overnight at 60 C. Water was added to the reaction liquid, and extracted with a mixed solvent of chloroform/methanol (10:1). The organic layer was dried with anhydrous magnesium sulfate, then the solvent was evaporated off under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, hexane:ethyl acetate=4:1 to 3:2) to obtain 6-iodo-1-(2-pyrrolidin-2-ylethyl)-1H-indazole (838 mg) and 6-iodo-2-(2-pyrrolidin-1-ylethyl)-2H-indazole (338 mg) successively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 68℃; for 3h; | Potassium carbonate (950 mg, 6.9 mmol) and potassium iodide (380 mg, 2.3 mmol) were added to a solution of 5-fluoro-3-iodo-indazole (600 mg, 2.3 mmol) and 1-(2-chloroethyl)pyrrolidine hydrochloride (779 mg, 4.6 mmol) in DMF (15 mL) at rt. The reaction was heated to 68 C. for 3 h and then allowed to cool to rt. The reaction was filtered, washing with MeOH, and the solution was concentrated. Purification by silica gel chromatography (10% MeOH/DCM) gave 720 mg (88%) of the title compound as a clear oil. This material contained a slight (minor isomer) impurity. 1H NMR (400 MHz, CDCl3): δ 1.76-1.81 (4H, m), 2.58-2.64 (4H, m), 3.05 (2H, t, J=7.3 Hz), 4.56 (2H, t, J=7.3 Hz), 7.10 (1H, dd, J=8.2, 4.7 Hz), 7.21 (1H, td, J=8.9, 2.3 Hz), 7.42 (1H, dd, J=9.1, 4.0 Hz). [M+H] calc'd for C13H15FIN3, 360. found, 360. |
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