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Chemical Structure| 175278-09-8 Chemical Structure| 175278-09-8

Structure of 175278-09-8

Chemical Structure| 175278-09-8

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Product Details of [ 175278-09-8 ]

CAS No. :175278-09-8
Formula : C7H5BrF3NO
M.W : 256.02
SMILES Code : NC1=CC=C(Br)C=C1OC(F)(F)F
MDL No. :MFCD00179338
InChI Key :QVILSWLYJYMGRN-UHFFFAOYSA-N
Pubchem ID :737382

Safety of [ 175278-09-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H317-H412
Precautionary Statements:P280-P301+P310
Class:6.1
UN#:2810
Packing Group:

Computational Chemistry of [ 175278-09-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 45.23
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

35.25 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.03
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

3.11
Log Po/w (WLOGP)?

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

4.2
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.

2.37
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

2.38
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.82

Water Solubility

Log S (ESOL):?

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

-3.6
Solubility 0.0649 mg/ml ; 0.000253 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.

-3.52
Solubility 0.0775 mg/ml ; 0.000303 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

-3.52
Solubility 0.077 mg/ml ; 0.000301 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.

-5.65 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

0.0
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

1.0 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<0.0
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)

1.74

Application In Synthesis of [ 175278-09-8 ]

* 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 [ 175278-09-8 ]

[ 175278-09-8 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 175278-09-8 ]
  • [ 87-13-8 ]
  • C15H15BrF3NO5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
at 135℃; for 2h; EXAMPLE 122 N-(4-Chlorobenzyl)-4-hydroxy-6-(3-hydroxy-1-propynyl)-8-(trifluoromethoxy)-3-quinolinecarboxamide [] A mixture of <strong>[175278-09-8]4-bromo-2-trifluoromethoxyaniline</strong> (10.0 g) and diethyl ethoxymethylenemalonate (7.9 mL) is heated to 135 C for 2 h. The reaction mixture is diluted with diphenylether (90 mL) and heated to reflux with removal of ethanol by a Dean-Start trap for 30 min. The resulting precipitate is poured into heptane and filtered to afford 10.83 g (73%) of the 6-bromo-8-trifluoromethoxyquinoline ethyl ester. A mixture of the quinoline ethyl ester (5.0 g) and 4-chlorobenzylamine (12.0 mL) are heated to 190 C for 1 h. The mixture is diluted with toluene (25 mL), allowed to cool to rt, and filtered. The crude product is recrystallized (HOAc, water) to afford 5.03 g (80%) of the amide. The resulting amide (469 mg), bis(triphenylphosphine)palladium (II) chloride (175 mg), and triethylamine (5.0 mL) are dissolved in DMF (50 mL). Propargyl alcohol (2.5 mL) is added over 20 h at 90 C. The reaction mixture was allowed to cool to rt, poured into aq. ammonium chloride (200 mL) and extracted with ethyl acetate (4 x 50 mL). The organic layer is washed with sat. aqueous brine (10 mL). The aqueous layer is back-extracted with ethyl acetate (20 mL). The combined organic layers are dried (MgSO4) and concentrated. The crude product is purified by column chromatography (dichloromethane/ methanol, 100/1; 50/1; 100/3) to afford 580 mg (26%) of the title compound as a white solid. Physical characteristics are as follows: Mp 262 C dec.1H NMR (DMSO-d6) delta 12.89, 10.12, 8.64, 8.20, 7.86, 7.42-7.34, 5.42, 4.55, 4.35.13C NMR (CF3CO2D) delta 175.7, 167.4, 144.1, 139.1, 134.8, 133.3, 131.5, 129.2, 129.1, 127.3, 126.3, 123.6, 123.2, 120.6, 107.3, 84.8, 84.1, 55.5, 44.1.IR (drift) 1936 (w), 1657 (s), 1602, 1574, 1544, 1517 (s), 1279 (s), 1268, 1223 (s), 1212 (s), 1183, 1161 (s), 1048, 1020, 802 cm-1.MS (ESI-) m/z 449 (M-H)-.Anal. Found for C21H14ClF3N2O4: C, 55.86; H, 3.16; N, 6.09; Cl, 7.96
  • 2
  • [ 175278-09-8 ]
  • [ 126747-14-6 ]
  • [ 885477-08-7 ]
YieldReaction ConditionsOperation in experiment
38% With sodium carbonate;5%-palladium/activated carbon; In methanol; water; at 70℃; for 12h; Step 1: A mixture of <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)benzenamine</strong> (512 mg, 2.0 mmol), 4-cyanophenylboronic acid (324 mg, 2.2 mmol), 5% activated palladium on carbon (50% wet, 100 mg) and sodium carbonate (424 mg, 4.0 mmol) in a mixture of methanol:water (20 mL, 1:1) was heated at 70 C. for 12 hours. The reaction mixture was filtered through a celite pad and the filtrate evaporated to give a crude residue. Purification on silica gel using a mixture of ethyl acetate:hexane (4:1) as eluant gave the light yellow solid 4-amino-3-trifluoromethoxy-biphenyl-4-carbonitrile (210 mg, 38% yield).
  • 3
  • [ 175278-09-8 ]
  • 4-bromo-1-chloro-2-(trifluoromethyloxy)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% NaNO2 (2.43 g, 0.035 mol) in water (10 mL) was added in portions over 30 min to <strong>[175278-09-8]4-bromo-2-trifluoromethoxyaniline</strong> (9 g, 35 mmol) in a mixture of HCl (aq, cone, 25 mL) and water (25 mL) at (0-2 0C). The mixture was stirred at 0-2 0C for 15 min and CuCl (6 g, 61 mmol) in HCl (aq, cone, 10 mL) was added dropwise. After 10 min at rt, the mixture was heated at reflux for 15 min. Steam-distillation followed by extraction (CH2Cl2), drying (Na2SO4) of the distillate followed by concentration and distillation (bp 82-84 0C at 20 Torr) gave 3.86 g (40%) of the sub-title compound.
40% NaNO2 (2.43 g, 0.035 mol) in water (10 mL) was added in portions over 30 min to <strong>[175278-09-8]4-bromo-2-trifluoromethoxyaniline</strong> (9g, 35 mmol) in a mixture of HCl (aq, cone,25 mL) and water (25 mL) at (0-2 0C). The mixture was stirred at 0-2 0C for 15 min and CuCl (6 g, 61 mmol) in HCl (aq, cone, 10 mL) was added dropwise. After EPO <DP n="136"/>10 min at it, the mixture was heated at reflux for 15 min. Steam-distillation followed by extraction (CHoCl2), drying (Na2SO4) of the distillate followed by concentration and distillation (bp 82-840C at 20 Torrj gave 3.86 g (40%) of the sub-title compound.
With copper dichloride; isopentyl nitrite; In acetonitrile; at 70℃; for 3h; A mixture of isoamyl nitrite (4 mL, 30 mmol), copper (II) chloride (3.22 g, 24 mmol) and <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (Compound 30A) (5.1 g, 20 mmol) in acetonitrile (80 mL) was heated at 70 C for 3 hours. The mixture was poured into an aqueous HC1 solution (0.5 M, 50 mL) and extracted with ethyl acetate (50 mL x 2). The combined extracts were washed with water (50 mL x 4) and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with flash column chromatography on silica gel (petroleum ether) to afford Compound 30B. LC-MS (ESI) m/z: non-ionizable compound under routine conditions used. ?H-NIVIR (DMSO-d6, 400 IVII{z): 5 (ppm) 7.33-7.3 5 (m, 1H), 7.37-7.40 (m, 1H), 7.48 (t, J= 1.6 Hz, 1H).
  • 4
  • [ 175278-09-8 ]
  • [ 7447-39-4 ]
  • 4-bromo-1-chloro-2-(trifluoromethyloxy)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tert.-butylnitrite; In acetonitrile; EXAMPLE 23A 4-bromo-1-chloro-2-(trifluoromethoxy)benzene A mixture of tert-butyl nitrite (1.78 mL, 15.0 mmol), copper (II) chloride (1.61 g, 12.0 mmol) and <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (2.56 g, 10.0 mmol) in acetonitrile (40 mL) was heated to 70 C., stirred for 3 hours, cooled to room temperature, poured into 0.5M HCl, and extracted with diethyl ether. The combined extracts were washed with water and brine, dried (MgSO4), filtered, and concentrated to provide the desired product. MS (ESI(+)) m/e 275 (M+H)+.
With tert.-butylnitrite; In acetonitrile; Example 23A 4-bromo-1-chloro-2-(trifluoromethoxy)benzene A mixture of tert-butyl nitrite (1.78 mL, 15.0 mmol), copper (II) chloride (1.61 g, 12.0 mmol) and <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (2.56 g, 10.0 mmol) in acetonitrile (40 mL) was heated to 70 C., stirred for 3 hours, cooled to room temperature, poured into 0.5M HCl, and extracted with diethyl ether. The combined extracts were washed with water and brine, dried (MgSO4), filtered, and concentrated to provide the desired product. MS (ESI(+)) m/e 275 (M+H)+.
  • 5
  • [ 175278-09-8 ]
  • [ 87-13-8 ]
  • [ 228728-40-3 ]
YieldReaction ConditionsOperation in experiment
10.83 g (73%) EXAMPLE 122 N-(4-Chlorobenzyl)-4-hydroxy-6-(3-hydroxy-1-propynyl)-8-(trifluoromethoxy)-3-quinolinecarboxamide STR160 A mixture of <strong>[175278-09-8]4-bromo-2-trifluoromethoxyaniline</strong> (10.0 g) and diethyl ethoxymethylenemalonate (7.9 mL) is heated to 135 C. for 2 h. The reaction mixture is diluted with diphenylether (90 mL) and heated to reflux with removal of ethanol by a Dean-Start trap for 30 min. The resulting precipitate is poured into heptane and filtered to afford 10.83 g (73%) of the 6-bromo-8-trifluoromethoxyquinoline ethyl ester.
  • 6
  • [ 860617-71-6 ]
  • [ 175278-09-8 ]
  • 5-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With potassium fluoride;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In tetrahydrofuran; hexane; for 16h; <strong>[175278-09-8]4-Bromo-2-(trifluoromethoxy)aniline</strong> (1.3 g, 5.0 mmol), 5-cyano-1-methyl-1H-pyrrol-2-yl boronic acid (0.9 g, 6.0 mmol), potassium fluoride (0.96 g, 16.5 mmol), and tris(dibenzylideneacetone)dipalladium (0.12 g, 0.12 mmol) were placed in an oven dried flask under nitrogen and THF (12.5 mL) was added. Tri-t-butylphosphine (10 wt % in hexane) (0.356 mL, 0.24 mol) was added and the reaction was stirred for 16 hours. The reaction mixture was filtered through silica, rinsed with ethyl acetate, and concentrated. The crude product was pre-adsorbed onto the Celite reagent and purified via Isco chromatography (the Redisep column, silica, gradient 5-30% ethyl acetate in hexane) to afford 1.0 g (71%) of 5-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile. HPLC purity 98.2% at 210-370 nm, 9.6 min.; the Xterra RP18 instrument, 3.5%, 150×4.6 mm column, 1.2 mL/min., 85/15-5/95 (Ammon. Form. Buff. PH=3.5/ACN+MeOH) for 10 min., hold 4 min. MS (ES) m/z 281.
71% tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In tetrahydrofuran; hexane; for 16h; Example 58 5-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile <strong>[175278-09-8]4-Bromo-2-(trifluoromethoxy)aniline</strong> (1.3 g, 5.0 mmol), 5-cyano-1-methyl -1H-pyrrol-2-ylboronic acid (0.9 g, 6.0 mmol), potassium fluoride (0.96 g, 16.5 mmol), and tris(dibenzylideneacetone)dipalladium (0.12 g, 0.12 mmol) were placed in an oven dried flask under nitrogen and THF (12.5 mL) was added. Tri-t-butylphosphine (10 wt % in hexane) (0.356 mL, 0.24 mol) was added and the reaction was stirred for 16 hours. The reaction mixture was filtered through silica, rinsed with ethyl acetate, and concentrated. The crude product was pre-adsorbed onto the Celite reagent and purified via Isco chromatography (the Redisep column, silica, gradient 5-30% ethyl acetate in hexane) to afford 1.0 g (71%) of 5-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile. HPLC purity 98.2% at 210-370 nm, 9.6 min.; the Xterra RP18 instrument, 3.5mu, 150*4.6 mm column, 1.2 mL/min., 85/15-5/95 (Ammon. Form. Buff. PH=3.5/ACN+MeOH) for 10 min., hold 4 min. MS (ES) m/z 281.
  • 8
  • [ 175278-09-8 ]
  • [ 2252-44-0 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; sodium nitrite; In water; isopropyl alcohol;Product distribution / selectivity; 1b. Preparation of 1 -bromo-3-trifluoromethoxybenzene. 2579.53 g of 2-propanol and 1100 g of the product from stage Ia are placed in a 10 litre lined glass reactor with 4 necks and outlet on bottom, and a previously prepared solution of 382.52 g of NaNO2 in 766.18 g of water is added. 459.6 g of concentrated sulphuric acid are then metered slowly. The acids are diluted and the upper organic phase is separated from the lower aqueous phase. The organic phase is washed and a first organic phase and an upper aqueous phase are separated. The latter is further diluted with water until a second organic phase is released. This organic phase is added to the first and everything is washed again, separating an aqueous phase and an organic phase which, after being anhydrified with CaCl2, undergoes distillation to provide the product indicated in the title (final yield 84%). B.p. 156-158C/760 mmHg.
  • 9
  • [ 1535-75-7 ]
  • [ 175278-09-8 ]
YieldReaction ConditionsOperation in experiment
1a. Preparation of 4-bromo-2-trifluoromethoxyaniline (formula (IIIa). 3462 g of acetic acid and 1700 g of 2-trifluoromethoxyaniline are placed at room temperature in a 10 1 lined glass reactor with 4 necks, outlet on bottom, thermostat with brine cryostat, provided with mechanical agitation, bubble condenser and thermometer; the mixture is subsequently cooled to 0-5C and 1894.26 g of NBS are added, maintaining the temperature at 0-50C. At the end of the reaction the mixture is brought back to room temperature and the acetic acid is eliminated by distillation. The residue is washed with water, the phases are separated, the organic phase is neutralised with NaHCCbeta and the phases are separated again, the inorganic phase is washed with water and the product indicated in the title is isolated. B.p. 115C/30 mmHg.
With N-Bromosuccinimide; acetic acid; at 0 - 20℃; To a solution of 2-(trifluoromethoxy)aniline (318A) (2.655 mg, 15 mmol) in acetic acid (6 mL) was added NBS (2.94 g, 16.5 mmol) at 0 C and stirred at room temperature overnight. It was concentrated under reduced pressure. The residue was diluted with ethyl acetate (100 mL), washed with water (30 mL) and brine (30 mL), dried over anhydrous sodium sulfate, concentrated, and purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 20% v/v) to afford Compound 318B. LC-MS (ESI) m/z: 256 [M +H]+; 'H-NMR (CDCb, 400 MHz): d (ppm) 3.89 (s, 2H), 6.67 (d, J= 8.8 Hz, 1H), 7.18 (dd, J= 8.8, 2.4 Hz, 1H), 7.28 (d, J= 2.4 Hz, 1H).
  • 10
  • [ 109-01-3 ]
  • [ 175278-09-8 ]
  • [ 1034732-96-1 ]
YieldReaction ConditionsOperation in experiment
70% With lithium hexamethyldisilazane; DavePhos;tris-(dibenzylideneacetone)dipalladium(0); In tetrahydrofuran; for 1h;Inert atmosphere; Reflux; Tris(dibenzilideneacetone)dipalladium (1.1 g, 1.2 mmol), 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)-biphenyl (0.94 g, 2.4 mmol), <strong>[175278-09-8]4-bromo-2-trifluoromethoxy-phenylamine</strong> (30.7 g, 120 mmol) in THF (50 mL) were charged in a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. LiN(TMS)2 solution (1 M in THF, 288 mL) and N-methylpiperazine (26.7 mL, 194 mmol) were added and the reaction refluxed for 1 h. The reaction mixture was then allowed to cool to room temperature and filtered through a pad of celite. The organic phase was concentrated, the residue dissolved in DCM (200 ml) and washed with water (1 x 100 ml). The organic phases were dried over anhydrous Na?SCM, the solvent evaporated in vacuo and the crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10) to afford 23 g of 4-(4-methyl-piperazin-1-yl)-2- trifluoromethoxy-phenylamine (70% yield) as a light brown powder. MS calc: 276.1318; MS found: 276.1320
  • 11
  • [ 175278-09-8 ]
  • [ 1352342-49-4 ]
  • 12
  • [ 175278-09-8 ]
  • [ 1352338-53-4 ]
  • 13
  • [ 175278-09-8 ]
  • [ 1352338-54-5 ]
  • 14
  • [ 175278-09-8 ]
  • [ 762-21-0 ]
  • [ 1352342-47-2 ]
YieldReaction ConditionsOperation in experiment
In ethanol; for 5h;Reflux; 4-Bromo-2-trifluoromethoxy-phenylamine (13 g, 0.05 mol) and But-2-ynedioic acid diethyl ester (10.3 g, 0.12 mol) were dissolved in EtOH (120ml) in a 500 ml round bottom flask and refluxed. The reaction was monitored by LC-MS. 3 h later; 0.3 eq. but-2-ynedioic acid diethyl ester was added. At t = 5h, the reaction mixture was concentrated down to remove the solvent under vacuum, a thick oil was obtained and was used without purification for the next step. MS [M+H]+ = 426.
  • 15
  • [ 175278-09-8 ]
  • [ 762-21-0 ]
  • [ 1352342-48-3 ]
  • 16
  • [ 75-15-0 ]
  • [ 175278-09-8 ]
  • C15H8Br2F6N2O2S2 [ No CAS ]
  • 17
  • [ 175278-09-8 ]
  • [ 100-39-0 ]
  • [ 1386950-85-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetonitrile; for 20h;Reflux; EXAMPLE 647-(2,6-dichlorobenzyl)-5-{ [4-^iperazin- l -yl)-2-(trifluoromethoxy)phenyl]amino}pyrido[3,4- d]pyridazin-4-ol EXAMPLE 64A /V,N-dibenzyl-<strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> To a mixture of <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (5 g. 19.53 mmol) and potassium carbonate (8.09 g, 58.89 mmol) in acetonitrile (200 mL) was added (bromomethyl)benzene (6.96 mL, 58.59 mmol) and the mixture was refluxed for 20 hours. The mixture was filtered and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel (200-300 mesh) eluting with 5/1 petroleum ether/ethyl acetate to give the title compound. MS : 436 (M + H+).
With potassium carbonate; In acetonitrile; for 20h;Reflux; Example 45 4-(2,6-dichlorobenzyl)-6-{ [4-(piperazin-l -yl)-2-(trifluoromethoxy)phenyl]amino }- lH- imidazo|4,5-c]pyridine-7-carboxamide EXAMPLE 45A NN-dibenzyl-<strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> To a mixture of <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (5 g, 19.53 mmol) and potassium carbonate (8.09 g, 58.89 mmol) in acetonitrile (200 mL) was added(bromomethyl)benzene (6.96 mL, 58.59 mmol) and the mixture was refluxed for 20 hours. The mixture was filtered and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel (200-300 mesh) eluting with 5/1 petroleum ether/ethyl acetate to give the title compound. MS: 436 (M + H+).
  • 18
  • [ 175278-09-8 ]
  • [ 1386950-86-2 ]
  • 19
  • [ 175278-09-8 ]
  • [ 1374641-77-6 ]
  • 20
  • [ 175278-09-8 ]
  • [ 1489391-85-6 ]
  • 21
  • [ 175278-09-8 ]
  • [ 1489176-06-8 ]
  • 22
  • [ 175278-09-8 ]
  • [ 1489176-75-1 ]
  • 23
  • [ 175278-09-8 ]
  • [ 97-51-8 ]
  • [ 1577131-71-5 ]
YieldReaction ConditionsOperation in experiment
35% In ethanol; for 1h;Reflux; The title compound, (E)-2-(((4-bromo-2-(trifluoromethoxy)phenyl)imino)methyl)-4-nitrophenol, was prepared by reflux a mixture of a solution containing 2-hydroxy-5-nitrobenzaldehyde (0.0138 g, 0.082 mmol) in 20 ml ethanol and a solution containing <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (0.0211 g, 0.082 mmol) in 20 ml ethanol. The reaction mixture was stirred for 1 hunder reflux. The crystals of suitable for (E)-2-(((4-bromo-2-(trifluoromethoxy)phenyl)imino)methyl)-4-nitrophenol X-ray analysis were obtained from ethyl alcohol by slow evaporation (yield%35; m.p 198-200 C).
  • 24
  • [ 67-56-1 ]
  • [ 175278-09-8 ]
  • [ 201230-82-2 ]
  • [ 457097-93-7 ]
YieldReaction ConditionsOperation in experiment
54% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; at 100℃; under 15201.0 Torr; for 36h; To a solution of <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (10 g, 50.21 mmol) in methanol (150 mL) in a pressure tank reactor was added TEA (11.84 g, 117.01 mmol), Pd(dppf)Ci2 CH2Q2 (2.4 g, 2.94 mmol). Then the reactor was charged with CO (g) (20 atm). The resulting reaction was stirred for 1.5 days at 100C. Then it was diluted with water (200 mL), extracted with ethyl acetate (3 x 100 mL) and the organic layers combined and dried in an oven under reduced pressure. The resulting mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1 :50) to afford methyl 4- amino-3-(trifluoromethoxy)benzoate as yellow solid (5 g, 54%).
  • 25
  • [ 175278-09-8 ]
  • [ 1261444-00-1 ]
  • 26
  • [ 175278-09-8 ]
  • [ 886500-50-1 ]
  • 27
  • [ 175278-09-8 ]
  • [ 1607024-35-0 ]
  • 28
  • [ 175278-09-8 ]
  • [ 1607022-88-7 ]
  • 29
  • [ 175278-09-8 ]
  • [ 32315-10-9 ]
  • N-[5-(4-aminophenyl)pyridin-2-yl]-2,2-dimethylpropanamide [ No CAS ]
  • N-(5-{4-[([4-bromo-2-(trifluoromethoxy)phenyl]amino}carbonyl)amino]phenyl}pyridin-2-yl)-2,2-dimethylpropanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Triphosgene (0.09 g, 0.3 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.16 g, 0.7 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.12 mL, 0.89 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.12 mL, 0.89 mmol), compound (9) (0.2 g, 0.74 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 3:1) yielding (W1).
  • 30
  • [ 175278-09-8 ]
  • [ 82261-42-5 ]
  • [ 32315-10-9 ]
  • N-[4-bromo-2-(trifluoromethoxy)phenyl]-N'-(4-pyridin-3-ylphenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Triphosgene (0.14 g, 0.48 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.3 g, 1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.2 mL, 1.44 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.2 mL, 1.44 mmol), 4-pyridin-3-ylaniline (5) (0.2 g, 1.2 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 6:1) yielding (L1). yield 73%
  • 31
  • [ 175278-09-8 ]
  • [ 501-53-1 ]
  • benzyl N-[4-bromo-2-(trifluoromethoxy)phenyl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With magnesium oxide; In acetone; at 20℃; [00680] Intermediate 74a: Benzyl N-[4-bromo-2-(trifluoromethoxy)phenyl] carbamate [00681] Benzyl chioroformate (15.6lmL, 109.37mmol) was added to a stirred solution of 4-bromo- 2-(trifluoromethoxy)aniline (11.83mL, 78.l2mmol) and oxomagnesium (2.68g, 66.4mmol) in acetone (l6OmL). The resulting solution was stirred overnight at room temperature. The mixture was stirred over the weekend at room temperature and then added to water (400mL) and this was stirred for 2hours at room temperature. The resulting solid was filtered off, washed with water and dried in vacuo. The solid was then stirred in EtOAc (300mL) at 50 C and the insoluble magnesium salts filtered off. The filtrate was concentrated in vacuo to give benzyl N-[4-bromo-2- (trifluoromethoxy)phenyl]carbamate (28.27g, 72.65mmol, 93% yield) as a white solid which was used in the next step without further purification.1H NMR (DMSO-d6, 400MHz) O/ppm: 9.71 (1H, 5), 7.77 (1H, d, J= 4.7Hz), 7.64-7.57 (2H, m),7.44 - 7.30 (5H, m) and 5.76 (2H, 5). MS Method 2: RT: 2.10 mi mlz 389.9 [M+H]
  • 32
  • [ 175278-09-8 ]
  • tert-butyl N-[4-(benzyloxycarbonylamino)-3-(trifluoromethoxy)phenyl]carbamate [ No CAS ]
  • 33
  • [ 175278-09-8 ]
  • benzyl N-[4-amino-2-(trifluoromethoxy)phenyl]carbamate [ No CAS ]
  • 34
  • [ 175278-09-8 ]
  • benzyl N-[4-(cyanomethylamino)-2-(trifluoromethoxy)phenyl]carbamate [ No CAS ]
  • 35
  • [ 175278-09-8 ]
  • benzyl N-{4-[(2-cyanocyclopent-1-en-1-yl)(cyanomethyl)amino]-2-(trifluoromethoxy)phenyl}carbamate [ No CAS ]
 

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