Structure of 1260383-51-4
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 1260383-51-4 |
Formula : | C9H8FN |
M.W : | 149.16 |
SMILES Code : | CC(N1)=CC2=C1C=CC=C2F |
MDL No. : | MFCD18380834 |
InChI Key : | PHGHGDMLJZDQIR-UHFFFAOYSA-N |
Pubchem ID : | 22490033 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.22 |
TPSA ? Topological Polar Surface Area: Calculated from |
15.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.85 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.68 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.04 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.31 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.41 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.66 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.06 |
Solubility | 0.13 mg/ml ; 0.000874 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.66 |
Solubility | 0.323 mg/ml ; 0.00217 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.93 |
Solubility | 0.0175 mg/ml ; 0.000117 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 |
-5.31 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 |
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) |
1.68 |
* 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 |
---|---|---|
0.19 g | With trifluoroacetic acid; In dichloromethane; at 20℃; for 24h; | Step 3a4-Fluoro-2-methylindole 1.43 ml of trifluoroacetic acid are added to a solution of 0.35 g of tert-butyl [3-fluoro-2-(2-oxopropyl)phenyl]carbamate in 13 ml of anhydrous dichloromethane at ambient temperature. The reaction mixture is then stirred at ambient temperature for 24 h, and is then diluted with 27 ml of dichloromethane and treated with 25 ml of a 5% sodium hydrogen carbonate solution. After stirring at ambient temperature for 1 hour and then settling out, the organic phase is separated and the aqueous phase is extracted with 25 ml of dichloromethane. The organic phases are combined, washed with saturated brine, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. 0.19 g of 4-fluoro-2-methylindole is thus obtained in the form of a dark red-colored oil, the characteristics of which are the following:1H NMR spectrum (400 MHz, CDCl3): 2.46 (s, 3H); 6.30 (broad m, 1H); 6.74 (dd, J=7.9 and 10.6 Hz, 1H); 7.02 (dt, J=4.9 and 7.9 Hz, 1H); 7.08 (d, J=7.9 Hz, 1H); 7.95 (broad m, 1H)Mass spectrometry: EI: [M]+. m/z=149 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.19 g | With sodium cyanoborohydride; acetic acid; at 14 - 20℃; for 2h;Inert atmosphere; | Step 4a4-Fluoro-2-methyl-2,3-dihydro-1H-indole 3.63 g of sodium cyanoborohydride are gradually added to a solution of 2.87 g of <strong>[1260383-51-4]4-fluoro-2-methylindole</strong> in 98 ml of acetic acid under argon cooled to a temperature of about 14 C. The reaction mixture is left to warm up to ambient temperature. After 2 hours, the reaction mixture is poured into a mixture of water and ice, and is then treated with a 28% aqueous ammonia solution until the pH is 9. The mixture is then extracted twice with dichloromethane. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified on a 300 g silica column, elution being carried out with a 100/0 to 90/10 v/v heptane/ethyl acetate gradient. 2.19 g of 4-fluoro-2-methyl-2,3-dihydro-1H-indole are thus obtained in the form of a colorless oil, the characteristics of which are the following:1H NMR spectrum (400 MHz): 1.18 (d, J=6.3 Hz, 3H); 2.49 (partially masked dd, J=7.6 and 15.7 Hz, 1H); 3.08 (dd, J=9.0 and 15.7 Hz, 1H); 3.92 (m, 1H); 5.87 (broad s, 1H); 6.20 to 6.31 (m, 2H); 6.90 (td, J=5.9 and 8.1 Hz, 1H)Mass spectrometry: method ARetention time Tr (min)=0.50;[M+H]+: m/z 152 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42.6% | With hydrogenchloride; In methanol; water; for 3h;Inert atmosphere; Reflux; | 1L reaction flask equipped with mechanical stirring, a condenser and a thermometer, under nitrogen atmosphere was added 53g indole reduction, 28g hydrochloric acid, 500mL methanol, 40mL water, warmed to reflux, incubated 3h. The mixture was concentrated under reduced pressure to dryness. 200 mL of water and 150 mL of ethyl acetate were extracted twice. The combined ethyl acetate layers were washed with water, dried and concentrated to dryness to give 34 g of an oily liquid. Purity: 99.8%, molar yield: 42.6%. |