Structure of 2026-70-2
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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. : | 2026-70-2 |
Formula : | C8H8F3N |
M.W : | 175.15 |
SMILES Code : | FC(C1=CC(NC)=CC=C1)(F)F |
MDL No. : | MFCD07368696 |
InChI Key : | SRTKIHVQZYXHHJ-UHFFFAOYSA-N |
Pubchem ID : | 2783214 |
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 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.75 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.03 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.95 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.71 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.71 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.51 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.75 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.87 |
Solubility | 0.236 mg/ml ; 0.00135 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.62 |
Solubility | 0.424 mg/ml ; 0.00242 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.72 |
Solubility | 0.0335 mg/ml ; 0.000191 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 |
-5.44 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) |
1.17 |
* 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 |
---|---|---|
EXAMPLE 19 10.74 g (26.3 mmol) of 1-cyano-1-[N-methyl-N-(3-trifluoromethylphenyl)carbamoyl]-2-[imino(4,4-dimethyl-2-oxo-1-imidazolidinyl)methylamino]ethene (compound IV) were placed in a flask which had been preheated to 190 C. and was closed with a distillation head. The substance was left, with magnetic stirring, at 190 C. for 5 minutes and at 190-192 C. for 6 min. The apparatus was then evacuated and the 3-methylaminobenzotrifluoride formed as by-product was substantially removed by distillation under vacuum at a bath temperature of 189 C.-175 C. over the course of 10 min. The resulting brown molten mass was taken up in 100 ml of CH2 Cl2, and this solution was extracted successively three times with 35 ml of 0.5N NaOH each time, twice with 20 ml of water each time and four times with 25 ml of 1N hydrochloric acid each time. | ||
With pyridine; copper diacetate; In 1,4-dioxane; for 6h;Reflux; | General procedure: Intermediate 1: N-Methyl-4-(trifluoromethyl) aniline To a mixture of 4-trifluoromethylaniline (196 mg, 1.2 mmol), copper acetate (550 mg, 3.0 mmol) and pyridine (0.34 mL, 4.2 mmol) in dioxane (6 mL) was added methylboronic acid (181 mg, 3.0 mmol, Aldrich, Catalog number: 165335). The mixture was heated with stirring under reflux for 6 hours. The resulting mixture was filtered. The filtrate was concentrated under vacuum and purified by column chromatography to afford N-methyl-4-(trifluoromethyl)-aniline (150 mg, 70 %). MS obsd. (ESI+) [(M+H)+]: 176 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(1w) 2-Nitro-N-methyl-N-[3-(trifluoromethyl)phenyl]benzamide, utilizing N-methyl-3-(trifluoromethyl)benzenamine prepared as described by Berbalk et al, Monatshefte Chemie 1976;107: 401-404, from 3-(trifluoromethyl)benzenamine, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In water; toluene; | Preparation of the starting compound STR39 To 6.8 g (0.039 mol) of <strong>[2026-70-2]N-methyl-3-trifluoromethylaniline</strong> in 50 ml of toluene there are added 5.4 ml (0.039 mol) of triethylamine and subsequently at 5 C., dropwise and with stirring, a solution of 5.4 g (0.039 mol) of methyl 2-chloro-2-hydroximino acetate in 17 g of toluene. The mixture is allowed to stand for 16 hours at room temperature, then washed twice with 50 ml of water each time, dried over sodium sulphate and concentrated in vacuo and the residue is chromatographed on silica gel (eluent: toluene/ethyl acetate 1:1). 0.5 g (4.6% of theory) of methyl 2-hydroximino-2-[N-methyl-N-(3-trifluoromethylphenyl)-amino]-acetate of melting point 131 C. are obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In ethyl acetate; N,N-dimethyl-formamide; | EXAMPLE 19 Preparation Of 4-(alpha,alpha,alpha-Trifluoro-N-methyl-m-toluidino)-6-[(alpha,alpha,alpha-trifluoro-m-tolyl)oxy]pyrimidine 4,6-Dichloropyrimidine (1.55 g, 0.01mol) and <strong>[2026-70-2]N-methyl-3-trifluoromethylaniline</strong> (2.0 g, 0.llmol) are combined and heated to 126 C under N2for 1.5 hours. The resulting oil is taken up in ethyl acetate, is washed with 10% sodium carbonate and dried over sodium sulphate. The organic phase is concentrated under reduced pressure to yield a yellow oil which is purified by column chromatography to give 4-chloro-6-(N-methyl-3-trifluoromethylanilino)-pyrimidine (1.78 g) as a white solid. 4-Chloro-6-(N-methyl-3-trifluoromethylanilino)-pyrimidine (0.30 g, 0.001 mol.) and sodium carbonate (0.28g, 0.003 mol.) in DMF are stirred for 10 minutes. m-Trifluoro-methylphenol (0.16g, 0.001mol) is added and the mixture is heated to 60 C for 12 hours. The mixture is then cooled and poured into water. The product is extracted into ethyl acetate, washed with 10% sodium hydroxide, 10% hydrochloric acid, and 5% potassium carbonate, dried over Na2SO4, filtered, and is concentrated under reduced pressure. 6-(N-methyl-3-trifluoromethylanilino)-4-(3-trifluoromethylphenoxy)pyrimidine (0.16g) obtained by chromatography as a white solid. M.p. 118-119 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethyl acetate; | EXAMPLE 19 Preparation Of 4-(alpha,alpha,alpha-Trifluoro-N-methyl-m-toluidino)-6-[(alpha,alpha,alpha-trifluorom-toly)oxy]pyrimidine 4,6-Dichloropyrimidine (1.55 g, 0.01 mol) and <strong>[2026-70-2]N-metyl-3-trifluoromethylaniline</strong> (2.0 g, 0.11 mol) are combined and heated to 126 C. under N2 for 1.5 hours. The resulting oil is taken up in ethyl acetate, is washed with 10% sodium carbonate and dried over sodium sulphate. The organic phase is concentrated under reduced pressure to yield a yellow oil which is purified by column chromatography to give 4-chloro-6-(N-methyl-3-trifluoromethylanilino)-pyrimidine (1.78 g) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | General procedure: S7 (0.35 g, 2 mmol) was dissolved in Et2O (5 mL) and converted into its hydrochloride salt by drop-wise addition of aq. HCl (1 M) in Et2O. The resulting precipitate was collected byfiltration, dried for 10 min, and used in the subsequent reaction. A mixture of S7 hydrochloride (212 mg, 1 mmol), S1 (185 mg, 1.1 mmol), and toluene (2 mL) was heated to 130 oC,stirred for 21 h, cooled to rt, and diluted with MeOH (5 mL). This solution was concentrated onto silicagel and purified on a silica gel column with gradient elution (EtOAc EtOAc-MeOH;4: 1 v/v). The fractions containing the desired guanidine were collected, concentrated under reduced pressure, andapplied to a second silica gel column eluted with Et3N-EtOAc-hexanes(5: 20: 75 by vol.) to afford 20 asa white solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In water; for 3h;Inert atmosphere; Reflux; | General procedure: To a solution of 3-(trifluoromethyl)aniline(5.0 g, 31 mmol) and trimethyl orthoformate (4.9 g, 46.5mmol) was added three drops of sulfuric acid.This mixture was slowly heated to 120 oC to allow MeOH to be distilled off, stirred for 2 h at 120 oC, heated to 170 oCfor 30 min, and cooled to 100 oC.Then aq. HCl (10%; 25 mL) was added.This mixture was then refluxed for 3 h, cooled to 0 oC (ice bath) and finally basified with aq. NaOH (20%).This solution was extracted with EtOAc (3 × 30 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The crudeproduct was purified on a silica gel column with gradient elution (hexanes hexane-EtOAc; 1: 10 v/v) to afford S7 as a colorless oil |
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