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Chemical Structure| 2026-70-2 Chemical Structure| 2026-70-2

Structure of 2026-70-2

Chemical Structure| 2026-70-2

N-Methyl-3-(trifluoromethyl)aniline

CAS No.: 2026-70-2

4.5 *For Research Use Only !

Cat. No.: A128248 Purity: 95%

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Product Details of [ 2026-70-2 ]

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

Safety of [ 2026-70-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 2026-70-2 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

12.03 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.95
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.71
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

3.71
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.88
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.51
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.75

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.87
Solubility 0.236 mg/ml ; 0.00135 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.62
Solubility 0.424 mg/ml ; 0.00242 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.72
Solubility 0.0335 mg/ml ; 0.000191 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.44 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.17

Application In Synthesis of [ 2026-70-2 ]

* 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.

  • Downstream synthetic route of [ 2026-70-2 ]

[ 2026-70-2 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 75-44-5 ]
  • [ 2026-70-2 ]
  • [ 55240-29-4 ]
  • 2
  • [ 463-71-8 ]
  • [ 2026-70-2 ]
  • Sodium; 1,2,3,4-tetrahydro-1,4-methano-naphthalen-6-olate [ No CAS ]
  • [ 51031-46-0 ]
  • 3
  • [ 2026-70-2 ]
  • C11H8ClNO4 [ No CAS ]
  • [ 67103-35-9 ]
  • 4
  • [ 2026-70-2 ]
  • [ 4318-56-3 ]
  • 3-methyl-6-<(3-trifluoromethylphenyl)methylamino>uracil [ No CAS ]
  • 5
  • [ 2026-70-2 ]
  • [ 97191-89-4 ]
  • C31H24F3N5O2 [ No CAS ]
  • 6
  • [ 351-36-0 ]
  • [ 74-88-4 ]
  • [ 2026-70-2 ]
  • 7
  • [ 2026-70-2 ]
  • [ 205694-39-9 ]
  • N-(3-Trifluoromethylphenyl)-N-methyl-2-[3-[N-(N-methyl-N-phenylcarbamoylmethyl)-N-[2-[3-(3-methylphenyl)ureido]acetyl]amino]phenoxy]acetamide [ No CAS ]
  • 8
  • [ 16516-12-4 ]
  • [ 2026-70-2 ]
  • [ 172896-57-0 ]
YieldReaction ConditionsOperation 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
  • 10
  • [ 77-78-1 ]
  • 3-trichloromethyl-aniline [ No CAS ]
  • [ 329-00-0 ]
  • [ 2026-70-2 ]
  • 11
  • [ 2026-70-2 ]
  • [ 13790-39-1 ]
  • N-(6,7-dimethoxyquinazolin-4-yl)-N-methyl-N-(3-trifluoromethylphenyl)amine hydrochloride [ No CAS ]
  • 12
  • [ 2026-70-2 ]
  • [ 147079-69-4 ]
  • 4-hydroxy-1-methyl-6-methylsulfanyl-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid methyl-(3-trifluoromethyl-phenyl)-amide [ No CAS ]
  • 13
  • [ 2026-70-2 ]
  • [ 248282-18-0 ]
  • 1,2-dihydro-4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[3-(trifluoromethyl)phenyl]-3-quinolinecarboxamide [ No CAS ]
  • 14
  • [ 2026-70-2 ]
  • N-(3-trifluoromethylphenyl)-N-methylthioacetamide [ No CAS ]
  • 15
  • [ 2026-70-2 ]
  • [ 172896-87-6 ]
  • 16
  • [ 98-16-8 ]
  • [ 2026-70-2 ]
YieldReaction ConditionsOperation 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,
  • 17
  • [ 30673-27-9 ]
  • [ 2026-70-2 ]
  • methyl 2-(hydroximino)-2-[N-methyl-N-(3-trifluoromethylphenyl)-amino]-acetate [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 18
  • [ 254895-36-8 ]
  • [ 1193-21-1 ]
  • [ 98-17-9 ]
  • [ 2026-70-2 ]
  • 4-(α,α,α,-Trifluoro-N-methyl-m-toluidino)-6-[(α,α,α-trifluoro-m-tolyl)oxy]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 19
  • [ 1193-21-1 ]
  • [ 2026-70-2 ]
  • [ 254895-36-8 ]
YieldReaction ConditionsOperation 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.
  • 20
  • [ 16169-88-3 ]
  • [ 2026-70-2 ]
  • C17H14F3N [ No CAS ]
  • [ 1240238-92-9 ]
  • 21
  • [ 2026-70-2 ]
  • [ 263268-63-9 ]
  • [ 1240238-93-0 ]
  • C21H16F3N [ No CAS ]
  • 23
  • [ 19836-78-3 ]
  • [ 2026-70-2 ]
  • [ 74418-14-7 ]
  • 25
  • [ 2026-70-2 ]
  • [ 7149-03-3 ]
  • [ 1295605-81-0 ]
  • 26
  • [ 2026-70-2 ]
  • [ 7149-03-3 ]
  • [ 1295605-47-8 ]
  • 27
  • [ 1019353-39-9 ]
  • [ 2026-70-2 ]
  • [ 1240693-62-2 ]
  • 28
  • [ 886362-73-8 ]
  • [ 2026-70-2 ]
  • [ 1240693-54-2 ]
  • 29
  • benzotriazol-1-ylmethyl-(3-trifluoromethyl-phenyl)-amine [ No CAS ]
  • [ 2026-70-2 ]
  • 30
  • [ 31555-60-9 ]
  • [ 2026-70-2 ]
  • [ 1396244-31-7 ]
  • 31
  • [ 2026-70-2 ]
  • [ 621-82-9 ]
  • N-methyl-N-(3-(trifluoromethyl)phenyl)cinnamamide [ No CAS ]
  • 32
  • [ 2026-70-2 ]
  • [ 21563-73-5 ]
  • 2-Amino-N'-methyl-N'-[3-(trifluoromethyl)phenyl]benzamide [ No CAS ]
  • 33
  • [ 2026-70-2 ]
  • [ 41279-57-6 ]
  • 1-methyl-3-(naphthalen-1-yl)-1-(3-(trifluoromethyl)phenyl)guanidine [ No CAS ]
YieldReaction ConditionsOperation 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
  • 34
  • C9H8F3NO [ No CAS ]
  • [ 2026-70-2 ]
  • 35
  • N-methyl-N-(3-(trifluoromethyl)phenyl)formamide [ No CAS ]
  • [ 2026-70-2 ]
YieldReaction ConditionsOperation 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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