Structure of 1041481-59-7
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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. : | 1041481-59-7 |
Formula : | C8H5FN2O2 |
M.W : | 180.14 |
SMILES Code : | O=C(C1=C(F)C2=C(NN=C2)C=C1)O |
MDL No. : | MFCD11007930 |
InChI Key : | CLNSDURQQKBHKP-UHFFFAOYSA-N |
Pubchem ID : | 22260727 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 43.01 |
TPSA ? Topological Polar Surface Area: Calculated from |
65.98 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.46 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.82 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.15 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.78 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.28 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.15 |
Solubility | 1.29 mg/ml ; 0.00714 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.16 |
Solubility | 1.24 mg/ml ; 0.0069 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.56 |
Solubility | 0.493 mg/ml ; 0.00274 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) |
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 |
-6.56 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 |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
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) |
1.5 |
* 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 |
---|---|---|
In tetrahydrofuran; DMF (N,N-dimethyl-formamide); for 0.75h; | To 1.65 g of 4-fluoro-1H-indazole-5-carbonitrile obtained by Production example 85, 8 mL of glacial acetic acid, 8 mL of water and 16 mL of concentrated sulfuric acid were added and stirred at 110C for 4 hours. After allowing the reaction solution to cool, 150 mL of ice water was added, and the precipitated carboxylic acid was collected by filtration. Under ice cooling, to a solution of the obtained carboxylic acid in N,N-dimethylformamide 12 mL-tetrahydrofuran 40 mL, a solution containing excess diazomethane in diethyl ether was added, and stirred at this temperature for 45 minutes. After distilling off the solvent under reduced pressure, the residue was dissolved in 100 mL of ethyl acetate, washed successively with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, to afford 1.98 g of the title compound as bright yellow crystals.1H-NMR ( 400 MHz, DMSO-D6 ) delta 3.87 ( 3H, s ), 7.45 ( 1H, d, J = 8.8 Hz ), 7.82 ( 1H, dd, J = 6.8, 8.8 Hz ), 8.36 ( 1H, s ), 13.70 ( 1H, s ) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; water; acetic acid; at 110.0℃; for 4.0h; | To 1.65 g of 4-fluoro-1H-indazole-5-carbonitrile obtained by Production example 85, 8 mL of glacial acetic acid, 8 mL of water and 16 mL of concentrated sulfuric acid were added and stirred at 110C for 4 hours. After allowing the reaction solution to cool, 150 mL of ice water was added, and the precipitated carboxylic acid was collected by filtration. Under ice cooling, to a solution of the obtained carboxylic acid in N,N-dimethylformamide 12 mL-tetrahydrofuran 40 mL, a solution containing excess diazomethane in diethyl ether was added, and stirred at this temperature for 45 minutes. After distilling off the solvent under reduced pressure, the residue was dissolved in 100 mL of ethyl acetate, washed successively with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, to afford 1.98 g of the title compound as bright yellow crystals.1H-NMR ( 400 MHz, DMSO-D6 ) delta 3.87 ( 3H, s ), 7.45 ( 1H, d, J = 8.8 Hz ), 7.82 ( 1H, dd, J = 6.8, 8.8 Hz ), 8.36 ( 1H, s ), 13.70 ( 1H, s ) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20.0℃; for 24.0h; | Step 1:400 mg of <strong>[1041481-59-7]4-fluoro-1H-indazole-5-carboxylic acid</strong>, 470 mg of 4-(3-methoxybenzyl)thiosemicarbazide and 468 mg of DAPECI are stirred for 24 hours at RT in 5 ml of DMF. The batch is poured into 1 N hydrochloric acid, and the resultant precipitate is filtered off with suction and dried, giving 410 mg of product [49%, MS-FAB (M+H+)=374.1; Rf (polar method): 1.69 min], which is employed in step 2 without further purification. |
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