Structure of 147619-40-7
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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. : | 147619-40-7 |
Formula : | C7H5ClN2O2 |
M.W : | 184.58 |
SMILES Code : | N#CC1=C(OC)C(Cl)=CNC1=O |
MDL No. : | MFCD07368155 |
InChI Key : | NSFMNXCAJNVYKF-UHFFFAOYSA-N |
Pubchem ID : | 10965211 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
65.88 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.39 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.17 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.4 |
Solubility | 7.42 mg/ml ; 0.0402 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.11 |
Solubility | 14.3 mg/ml ; 0.0774 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.76 |
Solubility | 0.319 mg/ml ; 0.00173 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 |
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 |
-7.31 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 |
1.0 |
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) |
1.98 |
* 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 |
---|---|---|
95% | With sulfuryl dichloride; acetic acid; at 10 - 54℃; for 4.5h; | 3-cyano-4-methoxy-2-H-pyridone (6.0 g, 0.04 mol)45ml glacial acetic acid into 250 ml three-necked flask,Cooling to below 15 ,Then 6.18 g (0.045 mol) g of sulfonyl chloride was added dropwise,Solution temperature control between 10 ~ 15 ,The rate of dropping can be controlled according to the temperature change.After dripping,Stirring for half an hour,Heating up to 52 ± 2 ,Insulation 50-54 reaction 4h,TLC (TLC developing agent: ethyl acetate: methanol = 9: 1) monitoring the reaction of raw materials is completed,The reaction solution was cooled to 20 ± 2 ° C,Stir for 2 hours,filter,The filter cake was washed with 58 ml of water,The wet product was dried at 80 ° C under normal pressure for 12 hours to dry,To give 7.01 g of 3-cyano-4-methoxy-5-chloro 2- (1H) pyridone as a white powder,Yield 95.0percentTheoretical yield 7.38g. |
92.7% | With thionyl chloride; at 0 - 5℃; for 6.0h;Reflux; | At a temperature of 0 ° C to 5 ° C,Sulfuryl chloride was slowly added dropwise to 3-cyano-4-methoxy-2 (1 H) pyridone, the temperature was not more than 5 ° C, the rate of thionyl chloride dropping was 1.5 ml / min, Raise the temperature to produce reflux,The reaction was carried out for 6 hours, and the thionyl chloride was evaporated to dryness under reduced pressure,Add 1 ml of n-hexane solid beating 1 hour, filter, dry, that is, too. Yield 92.7percent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.2% | With hydrogen bromide;Reflux; | Add in 250ml three-necked flask5-chloro-4-methoxy-3-cyano-2- (1H) pyridone,48percent hydrobromic acid 150 ml,Heating reflux reaction for about 20-24 hours,Stop the reaction, this time the system is dark red solution.The reaction solution was concentrated at 90-95 ° C under reduced pressure to dryness,Add 200ml purified water beating,After stirring for 1 hour, the filtrate was filtered.Filter cake in 55-60 blast drying,Brown solid,That gimeracil,Weight 6.57 g, yield 83.2percentPurity of 99.91percent (see Figure 1), |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.4% | Add in 100ml three-necked flask5-chloro-4-methoxy-3-cyano-2- (1H) pyridone,48percent hydrobromic acid 40 ml,Heated to 70-80 ° C dissolved,Reaction for about 1-2 hours,Generate a lot of solid,TLC monitors the reaction to the end.The reaction system was filtered,Wash the filter cake with a small amount of purified water.The filter cake was dissolved with 100 ml of a 3percent aqueous solution of potassium carbonate,And then pre-mixed with 4N hydrochloric acid to adjust the pH to 3-4,Precipitation of a large number of solid,After stirring for 0.5 hours,The filter cake was beaten with 5 ml of methanol and 50 ml of dichloromethane,After stirring for 0.5 hours,Filter cake in 55-60 blast drying,Get class white solid,That is, structural analogues E,Weight 4.3g, yield 50.4percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68.8% | With potassium carbonate; In N,N-dimethyl-formamide; at 5 - 40℃; | Add in 250 ml three-necked flask5-Chloro-4-methoxy-3-cyano -2- (1H) pyridone 5.54 g,Potassium carbonate 6.22 g,DMF 120 ml,Stir evenly.Slowly add DMFdilutedDimethyl sulfate solution,Control the internal temperature at 5-15 ,After the dropwise addition, the reaction was raised to 35-40 ° C for 4-6 hours,TLC to monitor the reaction to the end,Add 30ml of concentrated ammonia to quench the reaction.The reaction solution was added to 1 L of purified water,Precipitation of a large number of solid,Stir for 0.5 hours, suction filter.The filter cake was beaten twice with 200 ml of 5percent potassium carbonate solution,Filtration, TLC showed a single spot.The filter cake was dried at 55-60 ° C for 6 hours,A white solid,I.e., 5-chloro-4-methoxy-3-cyano-1-methyl -2- (1H) -pyridone, weight 4.1g,Yield 68.8percent. |
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