Structure of 660845-30-7
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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. : | 660845-30-7 |
Formula : | C6H5ClF2N2O |
M.W : | 194.57 |
SMILES Code : | O=CC1=C(Cl)N(C)N=C1C(F)F |
MDL No. : | MFCD12827692 |
InChI Key : | NMYPMEAFQUDCSC-UHFFFAOYSA-N |
Pubchem ID : | 19754692 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 38.95 |
TPSA ? Topological Polar Surface Area: Calculated from |
34.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.56 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.31 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.97 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.03 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.64 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.05 |
Solubility | 1.74 mg/ml ; 0.00895 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.64 |
Solubility | 4.42 mg/ml ; 0.0227 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.97 |
Solubility | 2.07 mg/ml ; 0.0106 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 |
-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 |
0.55 |
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) |
1.89 |
* 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 |
---|---|---|
3.2 g | With dihydrogen peroxide; sodium hydroxide In water; toluene at 37 - 50℃; for 7 h; | In a 500 ml flask, 6.0 g (31 mmol) of 5-chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehyde are added to 30 ml of toluene. A solution of 2.4 g (62 mmol) of sodium hydroxide in 6 ml of water is added to the reaction mixture, followed by 103 ml of a 30percent solution of hydrogen peroxide in water, whilst keeping the temperature below 37° C. After the end of the addition, the reaction mixture is stirred at 50° C. for 7 hours. Once the reaction mixture is back to room temperature, the two phases are separated and the organic phase is extracted with 100 ml of water. The combined aqueous phases are acidified to pH 2 with aqueous hydrochloric acid. The resulting white precipitate is filtered, washed twice with 20 ml of water, and dried to yield 3.2 g of 5-chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm: 3.78 (s, 3H); 7.12 (t, 1H, JHF=53.60 Hz); 13.19 (s, 1H); IR (KBr): 1688 cm-1 (C=O); 2200-3200 cm-1 broad (hydrogen bond). |
40 g | With copper(II) oxide; sodium hydroxide In water at 25 - 30℃; for 15 h; | In 1000 mL reaction flask, 38.9g 3- difluoromethyl-1-methyl-5-chloro-4-carbaldehyde and 390ml of water, 8.4g of sodium hydroxide was added, followed by stirring, 1g of nano copper oxide, control of the reaction temperature is 25-30 ° C, air through an oxidation reaction 15 hours, starting material HPLC i.e.3- difluoromethyl-1-methyl-5-chloro-4-carbaldehyde , less than the total amount of an amount of 0.2percent; the reaction was stopped by filtration, recovery of copper catalyst. The reaction mixture was cooled to below 10 ° C, add 31percent hydrochloric acid to a pH of 1-2, the precipitated solid was filtered; the solid was washed with a small amount of water; and dried to give the product 3-methyl-5-fluoro-1- chloro-pyrazole-4-carboxylic acid 40g, HPLC content 99percent; LC-MS: m / e = 210. |
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