[ CAS No. 130365-87-6 ] {[proInfo.proName]}

Name: 130365-87-6|1-(2-Bromoethyl)-4-(trifluoromethyl)benzene|95%
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SKU: A260192
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Quality Control of [ 130365-87-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 130365-87-6 ]

Product Details of [ 130365-87-6 ]

CAS No. :	130365-87-6	MDL No. :	MFCD10567022
Formula :	C₉H₈BrF₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WTCVMJLGKMOROW-UHFFFAOYSA-N
M.W :	253.06	Pubchem ID :	14949941
Synonyms :

Calculated chemistry of [ 130365-87-6 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.33
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	49.09
TPSA :	0.0 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.12 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.56
Log Po/w (XLOGP3) :	3.83
Log Po/w (WLOGP) :	4.8
Log Po/w (MLOGP) :	4.4
Log Po/w (SILICOS-IT) :	4.18
Consensus Log Po/w :	3.95

Druglikeness

Lipinski :	1.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.97
Solubility :	0.0274 mg/ml ; 0.000108 mol/l
Class :	Soluble
Log S (Ali) :	-3.53
Solubility :	0.0754 mg/ml ; 0.000298 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.95
Solubility :	0.00284 mg/ml ; 0.0000112 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.75

Safety of [ 130365-87-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 130365-87-6 ]

* 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.

Upstream synthesis route of [ 130365-87-6 ]
Downstream synthetic route of [ 130365-87-6 ]

[ 130365-87-6 ] Synthesis Path-Upstream 1~6

1
[ 130365-87-6 ]
[ 2968-93-6 ]

Yield	Reaction Conditions	Operation in experiment
33%	With sodium bicarbonate; hydrogen bromide In 5,5-dimethyl-1,3-cyclohexadiene	(Second step) A mixture of 2-(4-trifluoromethylphenyl) ethylalcohol (19.0 g) obtained at the first step, 47percent hydrobromic acid (60 ml) and xylene (70 ml) was heated under reflux for 11 hours while removing water, followed by feeding the resulting solution into a saturated sodium hydrogen carbonate (100 ml), washing the resulting organic layer with water, drying over anhydrous magnesium sulfate, removing anhydrous magnesium sulfate, distilling off the solvent under reduced pressure and distilling the resulting residue under reduced pressure, to obtain colorless, oily 2-(4-trifluoromethylphenyl)ethyl bromide (8.43 g). B.p.: 66.5° to 70° C. (2 mmHg). Yield: 33percent.

Reference： [1] Patent: US5534187, 1996, A,

2
[ 2968-93-6 ]
[ 130365-87-6 ]

Yield	Reaction Conditions	Operation in experiment
74%	at 100℃; for 2 h;	Step ii: l-(2-bromoethyl)-4-(trifluoromethyl)benzene To a 50 mL round bottom flask, were added 2-(4-(trifluoromethyl)phenyl)ethanol (7.9 g, 0.0415 mol) and phosphorous tribromide (5.6 g, 0.0207 mol). The reaction mixture was stirred at 100 °C for 2 h. To the reaction mixture, ice cold water was added. The reaction mixture was extracted with hexane. The organic layer was separated, washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to get crude product. The crude product was purified by column chromatography using 60-120 silica gel and 0-5 percent ethyl acetate in hexane to get the title compound [7.8 g, 74 percent].H NMR (300 MHz, CDCI3): δ 7.60 (d, 2H), 7.35 (d, 2H), 3.61 (t, 2H), 3.25 (t, 2H).

Reference： [1] Patent: WO2015/101928, 2015, A1, . Location in patent: Page/Page column 127;
[2] Patent: WO2005/123748, 2005, A1, . Location in patent: Page/Page column 97-98
[3] Patent: WO2005/49613, 2005, A1, . Location in patent: Page/Page column 48-49
[4] Patent: WO2007/69986, 2007, A1, . Location in patent: Page/Page column 87

3
[ 402-50-6 ]
[ 130365-87-6 ]

Reference： [1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 24, p. 5622 - 5626

4
[ 455-19-6 ]
[ 130365-87-6 ]

Reference： [1] Patent: EP718264, 1996, A1,

5
[ 32857-62-8 ]
[ 130365-87-6 ]

Reference： [1] Canadian Journal of Chemistry, 1996, vol. 74, # 3, p. 453 - 456
[2] Patent: WO2015/101928, 2015, A1,

6
[ 130365-87-6 ]
[ 141776-91-2 ]

Reference： [1] Bulletin of the Chemical Society of Japan, 1998, vol. 71, # 6, p. 1401 - 1407

[ 130365-87-6 ] Synthesis Path-Downstream 1~88

1
[ 130365-87-6 ]
1-bromo-2-(2-bromo-4-(trifluoromethyl)phenyl)ethane [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 3116 - 3124

2
[ 32857-62-8 ]
[ 130365-87-6 ]

Reference： [1]Canadian Journal of Chemistry,1996,vol. 74,p. 453 - 456
[2]Patent: WO2015/101928,2015,A1
[3]Patent: WO2019/104011,2019,A1

3
[ 130365-87-6 ]
C₇H₅F₂⁽¹⁺⁾ [ No CAS ]
[ 141776-91-2 ]
C₉H₈F₃⁽¹⁺⁾ [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1998,vol. 71,p. 1401 - 1407

4
[ 130365-87-6 ]
[ 169139-31-5 ]
4-(2,3,5-tri-O-benzyl-β-D-ribofuranosyl)-1-[2-(4-trifluoromethylphenyl)ethyl]imidazole [ No CAS ]
5-(2,3,5-tri-O-benzyl-β-D-ribofuranosyl)-1-[2-(4-trifluoromethylphenyl)ethyl]imidazole [ No CAS ]

Reference： [1]Tetrahedron,2005,vol. 61,p. 11976 - 11985

5
[ 3034-62-6 ]
[ 130365-87-6 ]
[ 876926-08-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 268 - 277

6
[ 130365-87-6 ]
[ 927685-43-6 ]

Yield	Reaction Conditions	Operation in experiment
21%		5-aminosalicylic acid (0.51 g, 3.90 mmole) was added to N, N-dimethylformamide (20.0 ml) at room temperature under nitrogen atmosphere, and the reaction mixture was stirred. Triethylamine (0.50 ml) and tetrabutylammonium iodide (10.1 mg) were added, and stirred for 30 minutes. Then, l-(2- (bromoethyl) -4-trifluoromethyl) benzene was added, and stirred at room temperature for 3 hours. Ice was added to quench the reaction. Produced crystal was filtered, again stirred with acetone and hexane, and re-filtered. Filtered solid was dissolved in ethylacetate, washed with 0.5 N hydrochloric acid and brine, dried over magnesium sulfate anhydrous, and distilled in vacuo to give 0.54 g (21 % yield) of 2-hydroxy-5- (4- (trifluoromethyl) phenylethylamino) benzoic acid.1H NMR (DMSOd6) : 7.62 (d, 2H), 7.48 (d, 2H), 6.98 (d, IH), <n="30"/>6 . 88 ( q , IH ) , 6 . 76 ( d , IH ) , 3 . 24 ( t , 2H ) , 2 . 91 ( t , 2H )

Reference： [1]Patent: WO2007/119973,2007,A1 .Location in patent: Page/Page column 27-28

7
[ 130365-87-6 ]
1-{2-[4-(trifluoromethyl)phenyl]ethyl}-1H-imidazole [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 268 - 277

8
[ 130365-87-6 ]
[ 876926-12-4 ]

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 268 - 277
[2]Organic and Biomolecular Chemistry,2006,vol. 4,p. 268 - 277

9
[ 130365-87-6 ]
2-nitro-9-(trifluoromethyl)-5,6-dihydroimidazo[2,1-a]isoquinoline [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 268 - 277
[2]Organic and Biomolecular Chemistry,2006,vol. 4,p. 268 - 277

10
[ 130365-87-6 ]
6-(trifluoromethyl)-1-methyl-1-(trimethylsilyl)-1-silaindan [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 3116 - 3124

Yield	Reaction Conditions	Operation in experiment
32%		(Third step) A mixture of dry Mg (0.77 g, 0.032 mol), 2-(4-trifluoromethylphenyl)ethyl bromide (8.0 g, 0.032 mol) obtained at the second step and diethyl ether (40 ml) was heated at 60 C. for one hour in a sealed tube reactor to obtain a gray, uniform solution, followed by adding this solution to a diethyl ether (30 ml) solution of 4-(4-pentylcyclohexyl)cyclohexanone (7.9 g, 0.032 mol), stirring the mixture at room temperature for 3 hours, feeding the resulting reaction substance into a saturated aqueous solution of NH4 Cl, twice extracting with ethyl acetate (50 ml), washing the resulting organic layer, with an aqueous solution of NaCl, drying over anhydrous MgSO4, removing anhydrous MgSO4, distilling off the solvent under reduced pressure, to obtain pale yellow, oily 1-(2-(4-trifluoromethylphenyl)ethyl)-4-(4-pentylcyclohexyl)cyclohexanol (11.4 g), adding thereto toluene (50 ml) and Amberlyst (0.7 g), heating the mixture under reflux for one hour, while removing water formed by the reaction, allowing the resulting substance to cool, feeding it to a saturated aqueous solution of NH4 Cl (100 ml), twice washing the resulting separated organic layer with water, drying over anhydrous magnesium sulfate, filtering off the anhydrous MgSO4, distilling off the solvent under reduced pressure, subjecting the resulting residue to column chromatography (silica gel, eluent: heptane) and twice recrystallizing from ethanol (20 ml), to obtain 1-(2 -(4-trifluoromethylphenyl)ethyl)-4-(4-pentylcyclohexyl)cyclohexene (4.1 g). Yield: 32%. Cr-S point 70.7 C., S-N point 81.5 C., N-Iso point 88.5 C. 1 H-NMR (CDCl3) delta (ppm):7.38 (dd, 4H), 5.40 (brs, 1H), 2.67 (t, 2H), 2.31-0.81 (m, 30H) MS: 406 (M+)

13
[ 455-19-6 ]
sodiumboronhydride [ No CAS ]
[ 130365-87-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen bromide; sodium hydrogencarbonate; In ethanol; water;	(Third step) Ethanol (200 ml) was added to the above 4-trifluoromethylbenzylaldehyde (17.5 g, 93 mmol), followed by cooling the mixture down to 0C in a nitrogen atmosphere, adding thereto sodiumboronhydride (1.78 g, 47.1 mmol) so that the liquid temperature might not exceed 10C, stirring the mixture at 0C for 2 hours, extracting the resulting product with ethyl acetate, washing the organic layer successively with a saturated, aqueous solution of sodium bicarbonate and water, drying over magnesium sulfate, distilling off the solvent, adding an aqueous solution of HBr (47%) (100 ml) to the residue (about 18 g), refluxing the mixture for 7 hours and distilling under reduced pressure by means of Vigoureux tube, to obtain 2-(4-trifluoromethylphenyl)bromoethane (19.5 g, 77.1 mmol) (b.p.: 94C under 9 Torr). Yield: 82.9%.

Reference： [1]Patent: EP718264,1996,A1

14
[ 89-57-6 ]
[ 130365-87-6 ]
[ 927685-43-6 ]

Yield	Reaction Conditions	Operation in experiment
21%		5-aminosalicylic acid (0.51 g, 3.90 mmole) was added to N,N-dimethylformamide (20.0 ml) at room temperature under nitrogen atmosphere, and the reaction mixture was stirred. Triethylamine (0.50 ml) and tetrabutylammonium iodide (10.1 mg) were added, and stirred for 30 minutes. Then, 1-(2-(bromoethyl)-4-trifluoromethyl)benzene was added, and stirred at room temperature for 3 hours. Ice was added to quench the reaction. Produced crystal was filtered, again stirred with acetone and hexane, and re-filtered. Filtered solid was dissolved in ethylacetate, washed with 0.5 N hydrochloric acid and brine, dried over magnesium sulfate anhydrous, and distilled in vacuo to give 0.54 g (21% yield) of 2-hydroxy-5-(4-(trifluoromethyl)phenylethylamino)benzoic acid.1H NMR (DMSO-d6): 7.62 (d, 2H), 7.48 (d, 2H), 6.98 (d, 1H) 6.88 (q, 1H), 6.76 (d, 1H), 3.24 (t, 2H), 2.91 (t, 2H)

Reference： [1]Patent: US2009/240079,2009,A1 .Location in patent: Page/Page column 7

15
[ 1201195-37-0 ]
[ 130365-87-6 ]
[ 1201195-35-8 ]

Yield	Reaction Conditions	Operation in experiment
33%		To a solution of N-(2,5-dimethyl-2H-pyrazol-3-yl)-2-oxo-2-phenyl-acetamide (200 mg, 0.82 mmol) in DMF (2 mL) was added at 0 C. potassium bis(trimethylsilyl)amide (0.91 M in THF, 1.1 mL, 0.99 mmol) over a period of 5 min. The ice bath was removed and the solution was stirred for 1 h at ambient temperature. After the addition of 1-(2-bromo-ethyl)-4-trifluoromethyl-benzene (which might be prepared according to WO2005123748, 250 mg, 0.99 mmol) the reaction mixture was stirred for 18 h at ambient temperature. After the addition of cesium carbonate (1.40 g, 4.11 mmol) and further 1-(2-bromo-ethyl)-4-trifluoromethyl-benzene (996 mg, 3.95 mmol) it was stirred for 20 h at ambient temperature. The resulting mixture was diluted with TBME (15 mL) and washed twice with water (10 mL) and brine (10 mL). The combined aqueous layers were extracted with TBME (15 mL) and the combined organic layers were dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 60:40) afforded the title compound (113 mg, 33%) as a light brown oil. MS m/e: 416.3 [M+H]+.

Reference： [1]Patent: US2009/312314,2009,A1 .Location in patent: Page/Page column 37

16
C₁₄H₁₂N₂O₂ [ No CAS ]
[ 130365-87-6 ]
[ 1201195-44-9 ]

Yield	Reaction Conditions	Operation in experiment
18%	With caesium carbonate; In tetrahydrofuran; for 21h;Inert atmosphere;	To a suspension of N-(6-chloro-pyridin-3-yl)-2-oxo-2-phenyl-acetamide (0.39 g, 1.64 mmol) and cesium carbonate (2.6 g, 8.2 mmol) in THF (5 mL) was added under a nitrogen atmosphere over a period of 3 h 1-(2-bromo-ethyl)-4-trifluoromethyl-benzene (which might be prepared according to WO2005123748, 1.20 g, 4.9 mmol). The reaction mixture was stirred for 18 h at ambient temperature. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=50:50 to 30:70) afforded the title compound (120 mg, 18%) as a white solid. MS m/e: 413.1 [M+H]+.

Reference： [1]Patent: US2009/312314,2009,A1 .Location in patent: Page/Page column 38

17
[ 1201195-29-0 ]
[ 130365-87-6 ]
[ 1201195-27-8 ]

Yield	Reaction Conditions	Operation in experiment
6%		To a suspension of (R,S)-[(4-chloro-phenyl)-(2,5-dimethyl-2H-pyrazol-3-ylcarbamoyl)-methyl]-carbamic acid tert-butyl ester (600 mg, 1.58 mmol) and potassium carbonate (1.09 g, 7.91 mmol) in DMF (4 mL) was added under vigorously stirring at 90 C. a solution of 1-(2-bromo-ethyl)-4-trifluoromethyl-benzene (which might be prepared according to WO2005123748, 600 mg, 2.38 mmol) in DMF (2 mL) over a period of 1 h and stirring was continued for further 30 min. at 90 C. Further 1-(2-bromo-ethyl)-4-trifluoromethyl-benzene (600 mg, 2.38 mmol) in DMF (2 mL) was added over a period of 1 h and stirring was continued for further 18 h at 90 C. After cooling to ambient temperature the solution was diluted with ethyl acetate (20 mL) and washed with aqueous sodium carbonate (half saturated, 20 mL) and twice with brine (20 mL). The combined aqueous layers were extracted with ethyl acetate (20 mL) and the combined organic layers were dried over sodium sulfate. The concentrated filtrate was treated with TFA (1 mL, 13 mmol) and stirred for 3 h at ambient temperature. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate:methanol=90:10:0 to 50:45:5) afforded the title compound (43 mg, 6%) as a light brown oil. MS m/e: 451.0 [M+H]+.

Reference： [1]Patent: US2009/312314,2009,A1 .Location in patent: Page/Page column 35

18
[ 130365-87-6 ]
[ 178685-14-8 ]

Reference： [1]Steroids,2010,vol. 75,p. 330 - 337

19
[ 1194-98-5 ]
[ 130365-87-6 ]
[ 1311393-07-3 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4490 - 4507

20
[ 130365-87-6 ]
[ 1311392-82-1 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4490 - 4507

21
[ 130365-87-6 ]
[ 1311393-08-4 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4490 - 4507

22
[ 1361323-32-1 ]
[ 130365-87-6 ]
[ 1361323-52-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; sodium iodide; In acetonitrile; at 60℃;	General procedure: A mixture of tert-butyl (S)-1-((S)-3,3-dimethyl-1-oxo-1-((S)-piperidin-3-ylamino)butan-2-ylamino)-1-oxopropan-2-yl(methyl)carbamate (Intermediate 49; 100 mg, 0.25 mmol), 1-bromo-4-(2-bromoethyl)benzene (66 mg, 0.25 mmol), sodium bicarbonate (63 mg, 0.75 mmol) and sodium iodide (9.4 mg, 0.06 mmol) in acetonitrile (3.0 mL) was heated at 60 C overnight. The mixture was allowed to cool and was concentrated under reduced pressure. The residue was partitioned between EtOAc and water, and the organic layer was concentrated. The crude material was purified by reverse phase HPLC (gradient of 40-70% MeCN in H2O containing 0.2% NH4OH) to give the product as a sticky gum.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1690 - 1694

23
[ 1361323-32-1 ]
[ 130365-87-6 ]
[ 1361322-74-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1690 - 1694

24
[ 1382354-46-2 ]
[ 130365-87-6 ]
[ 1382354-24-6 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 5760 - 5773

25
[ 17356-08-0 ]
[ 130365-87-6 ]
C₁₀H₁₁F₃N₂S*BrH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; for 2h;Reflux;	General procedure: Thiourea (7 mmol) was dissolved in 13.5 mL ethanol and the appropriate alkylbromide (7 mmol) was added. The mixture was stirred and heated under reflux for 2 h after which the reaction became homogenous. The reaction was allowed to cool to room temperature and the ethanol solvent was removed under reduced pressure. A solution of NaOH (10.5 mmol) in 8.75 mL water was added to the residue, and the reaction mixture was heated under reflux (120 C) for 2 h. The reaction was subsequently cooled to room temperature and aqueous H2SO4 (15%) was added. The mercaptan separated as oil droplets and was extracted to diethylether (30 mL). The organic phase was washed twice with water, dried over anhydrous Na2SO4 and removed under reduced pressure. This yielded the desired mercaptans which were used without further purification for the synthesis of 1, 3 and 4.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 7040 - 7050

26
[ 130365-87-6 ]
[ 1415676-38-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 7040 - 7050

27
[ 130365-87-6 ]
[ 1267391-25-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 7040 - 7050

28
[ 130365-87-6 ]
[ 864528-17-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium azide; In dimethyl sulfoxide; at 20℃;	General procedure: To a solution of the appropriatehalide (7a-c, 9a-f or 11b-h) in 2ml of DMSO NaN3is added and the solution was stirred overnight. Then, 6,CuSO4*5H2O (0.2 eq), sodium ascorbate (0.10 eq), and 2mlof distilled water are added to the solution and the solutionwas stirred overnight. The solution is diluted in water andthe mixture is extracted 3 times with EtOAc. The combinedorganic phase is washed twice with a solution of NH4Cl5Mand then twice with brine. The combined organic phaseis dried with MgSO4, to afford the crude product. Thepurification was performed as stated for each compound.

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9562 - 9575
[2]Angewandte Chemie - International Edition,2013,vol. 52,p. 8031 - 8036
Angew. Chem.,2013,vol. 125,p. 8189 - 8194,6
[3]Journal of Chemistry,2017,vol. 2017

29
[ 130365-87-6 ]
[ 1316652-10-4 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9562 - 9575

30
4a-phenethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol [ No CAS ]
[ 130365-87-6 ]
4a-phenethyl-2-(4-(trifluoromethyl)phenethyl)-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 50℃; for 20h;	General procedure: A mixture of the amine 9, alkyl bromide (1.2 equiv) and NaHCO3 (2 equiv) in DMF (20 mL) was heated at 50 C for 20 h. After cooling to room temperature, the reaction mixture was poured into ice-H2O, and the product was extracted with Et2O. The ethereal extracts were washed with saturated NH4Cl solution. After drying over Na2SO4, the solvent was removed in vacuo to afford an oil. The crude oil was subjected to flash chromatography on silica gel using 75% EtOAc in hexanes as the eluent to give the compounds 3a-h as a solid.

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 3298 - 3309

31
[ 130365-87-6 ]
N-tert-butyl-4-nitro-2-[4-(trifluoromethyl)phenethylamino]benzamide [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 8031 - 8036
Angew. Chem.,2013,vol. 125,p. 8189 - 8194,6

32
[ 130365-87-6 ]
[ 1508310-43-7 ]

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 65 - 68

33
[ 130365-87-6 ]
[ 1508310-45-9 ]

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 65 - 68

34
[ 130365-87-6 ]
[ 1508310-64-2 ]

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 65 - 68

35
[ 130365-87-6 ]
[ 1508310-42-6 ]

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 65 - 68

36
[ 130365-87-6 ]
[ 106-50-3 ]
[ 1508310-59-5 ]

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 65 - 68

37
[ 6146-52-7 ]
[ 130365-87-6 ]
[ 1508310-63-1 ]

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 65 - 68

38
[ 115-46-8 ]
[ 130365-87-6 ]
diphenyl(1-(4-(trifluoromethyl)phenethyl)piperidin-4-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With triethylamine; In acetonitrile; at 85℃; for 18h;	Diphenyl(1-(4-(trifluoromethyl)phenethyl)piperidin-4-yl)methanol To a vial was added the diphenyl(piperidin-4-yl)methanol (0.100 g, 0.374 mmol), <strong>[130365-87-6]1-(2-bromoethyl)-4-(trifluoromethyl)benzene</strong> (0.057 ml, 0.340 mmol) and acetonitrile (10 mL). The TEA (0.071 mL, 0.510 mmol) was then added and the reaction stirred at 85 C. for 18 h. The reaction was diluted with water and extracted with EtOAc (3*15 mL). The EtOAc layer was collected and dried with MgSO4, filtered and adsorbed to silica then purified by MPLC (15 min, 0-10% MeOH:DCM) to produce pure diphenyl(1-(4-(trifluoromethyl)phenethyl)piperidin-4-yl)methanol (0.074 g, 0.168 mmol, 49% yield) as an oil. 1H NMR (400 MHz, CDCl3): delta 7.54-7.47 (m, 4H), 7.33-7.27 (m, 6H), 7.19 (tt, J=7.3 Hz, 1.8 Hz, 2H), 3.06-3.00 (m, 2H), 2.86-2.80 (m, 2H), 2.60-2.55 (m, 2H), 2.51-2.42 (m, 1H), 2.14 (br s, 1H), 2.10-2.03 (m, 2H), 1.57-1.47 (m, 4H). 13C NMR (125 MHz, CDCl3): delta 145.9, 144.6, 129.0, 128.3 (q, J=32 Hz), 128.2, 126.5, 125.8, 125.2 (q, 3.8 Hz), 124.2 (q, J=271.8 Hz), 79.5, 60.2, 54.1, 44.1, 33.6, 26.4, 21.0. LCMS Retention time: 3.877 min. LCMS purity 99.1%. HRMS (ESI): m/z calcd for C27H28F3NO [M+H]+ 440.2123. found 440.2196.

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 8540 - 8562
[2]Patent: US2015/238473,2015,A1 .Location in patent: Paragraph 0266

39
4a-(3-phenylpropyl)-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol [ No CAS ]
[ 130365-87-6 ]
4a-(3-phenylpropyl)-2-(4-(trifluoromethyl)phenethyl)-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 50℃; for 20h;	General procedure: A mixture of the amine 9, alkyl bromide (1.2 equiv) and NaHCO3 (2 equiv) in DMF (20mL) was heated at 50C for 20h. After cooling to room temperature, the reaction mixture was poured into ice- H2O, and the product was extracted with Et2O. The ethereal extracts were washed with saturated NH4Cl solution, dried over Na2SO4, and the solvent was removed in vacuo to afford an oil. The crude oil was subjected to flash chromatography on silica gel using 75% EtOAc in hexanes as the eluent to give the 10-12 as solids.

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 92,p. 531 - 539

40
4a-(4-phenylbutyl)-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol [ No CAS ]
[ 130365-87-6 ]
4a-(4-phenylbutyl)-2-(4-(trifluoromethyl)phenethyl)-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 50℃; for 20h;	General procedure: A mixture of the amine 9, alkyl bromide (1.2 equiv) and NaHCO3 (2 equiv) in DMF (20mL) was heated at 50C for 20h. After cooling to room temperature, the reaction mixture was poured into ice- H2O, and the product was extracted with Et2O. The ethereal extracts were washed with saturated NH4Cl solution, dried over Na2SO4, and the solvent was removed in vacuo to afford an oil. The crude oil was subjected to flash chromatography on silica gel using 75% EtOAc in hexanes as the eluent to give the 10-12 as solids.

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 92,p. 531 - 539

41
4a-(5-phenylpentyl)-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol [ No CAS ]
[ 130365-87-6 ]
4a-(5-phenylpentyl)-2-(4-(trifluoromethyl)phenethyl)-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 50℃; for 20h;	General procedure: A mixture of the amine 9, alkyl bromide (1.2 equiv) and NaHCO3 (2 equiv) in DMF (20mL) was heated at 50C for 20h. After cooling to room temperature, the reaction mixture was poured into ice- H2O, and the product was extracted with Et2O. The ethereal extracts were washed with saturated NH4Cl solution, dried over Na2SO4, and the solvent was removed in vacuo to afford an oil. The crude oil was subjected to flash chromatography on silica gel using 75% EtOAc in hexanes as the eluent to give the 10-12 as solids.

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 92,p. 531 - 539

42
[ 141-97-9 ]
[ 130365-87-6 ]
[ 1058726-84-3 ]

Yield	Reaction Conditions	Operation in experiment
66%		Step-i: Synthesis of 5-(4-(trifluoromethyl)phenyl)pentan-2-one (11a) To a suspension of sodium metal (0.65 g, 0.0282 mol) in ethanol (20 mL) was added ethyl acetoacetate at RT, refluxed for an hour, then RM was cooled to RT. To this mixture was then added l-(2-bromoethyl)-4-(trifluoromethyl)benzene (7.5 g, 0.0296 mol) and refluxed for 12 h. The reaction mixture was then cooled to RT, filtered. Solids washed with ethanol, filtrate concentrated to get residue. To the residue obtained was added 5% NaOH (30 mL) and heated to 90 C for 5 h, then cooled to RT. This mixture was again treated with 50% sulphuric acid (13 mL) and heated to 90 C for 5 h, cooled to RT, diluted with water, extracted into diethyl ether. The organic portion was washed with water and brine solution, then, dried over Na2S04, filterd and concentrated to get residue. The residue was purified by column chromatography over silica gel (60-120) using 10% ethyl acetate in hexane as to get the pure titled compound (4.5 g, 66%).
66%		Step iii: 5-(4-(trifluoromethyl)phenyl)pentan-2-one A 250 mL round bottom flask was charged with sodium (0.65 g, 0.0282 mol) and absolute ethanol (20 mL) and. To the same flask, ethyl acetoacetate (3.7 g, 0.0282 mol) was added. The resulting reaction mixture was stirred at reflux temperature for 1 h. The reaction mixture was cooled to room temperature. To the same flask, l-(2-bromoethyl)-4-(trifluoromethyl)benzene (7.5 g, 0.0296 mol) was added. The reaction mixture was stirred at reflux temperature for 12 h. The reaction mixture was cooled to room temperature to get solid. The solid was removed by filtration. The filtrate was evaporated under reduced pressure to get residue. To the residue, 5 % aqueous sodium hydroxide (30 mL) was added. The reaction mixture was stirred at 90 C for 5 h and cooled to room temperature. To the same flask, 50 % aqueous sulfuric acid (13 mL) was added. The reaction mixture was stirred at 90 C for 5 h and cooled to room temperature. The reaction mixture was diluted with water and extracted with hexane. The reaction mixture was extracted with diethyl ether. The organic layer was separated, washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to get crude product. The crude product was purified by column chromatography using 60-120 silica gel and 0-10 % ethyl acetate in hexane to get the title compound [4.5 g, 66 %]. *H NMR (300 MHz, CDCI3): delta 7.55 (d, 2H), 7.29 (d, 2H), 2.70 (t, 2H), 2.47 (t, 2H), 1.96-1.86 (m, 2H), 2.13 (s, 3H).

Reference： [1]Patent: WO2015/83130,2015,A1 .Location in patent: Page/Page column 34-35
[2]Patent: WO2015/101928,2015,A1 .Location in patent: Page/Page column 127;

43
[ 130365-87-6 ]
2-(4-(ethylsulfonyl)phenyl)-N-(7-oxo-6-(4-(trifluoromethyl)phenethyl)-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)acetamide [ No CAS ]

Reference： [1]Patent: WO2015/101928,2015,A1

44
[ 130365-87-6 ]
2-(4-(ethylsulfonyl)phenyl)-N-(6-(4-(trifluoromethyl)phenethyl)-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)acetamide [ No CAS ]

Reference： [1]Patent: WO2015/101928,2015,A1

45
[ 130365-87-6 ]
4-(4-(trifluoromethyl)phenethyl)cyclohexane-1,3-dione [ No CAS ]

Reference： [1]Patent: WO2015/101928,2015,A1

46
[ 130365-87-6 ]
2-bromo-4-(4-(trifluoromethyl)phenethyl)cyclohexane-1,3-dione [ No CAS ]

Reference： [1]Patent: WO2015/101928,2015,A1

47
[ 130365-87-6 ]
2-amino-6-(4-(trifluoromethyl)phenethyl)-5,6-dihydrobenzo[d]thiazol-7(4H)-one [ No CAS ]

Reference： [1]Patent: WO2015/101928,2015,A1

48
[ 130365-87-6 ]
6-(4-(trifluoromethyl)phenethyl)-4,5,6,7-tetrahydrobenzo[d]thiazol-2-amine [ No CAS ]

Reference： [1]Patent: WO2015/101928,2015,A1

49
[ 1401938-80-4 ]
[ 130365-87-6 ]
(3'R,5'S,8'R,9'S,10'S,13'S,14'S)-10',13'-dimethyl-4"-{2-[4-(trifluoromethyl)phenyl]ethyl}tetradecahydro-2'H,6"H-dispiro[1,3-dioxolane-2,17'-cyclopenta[a]phenanthrene-3',2"-[1,4]oxazinan]-6"-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%		General procedure: To a solution of 4a-4e (0.1 mmol) in dry DCM (5 mL) was addedDIPEA (0.17 mmol) in a Schlenk tube. The tube was screwed down,stirred and heated at 75 C for 10 min, and the reaction mixturewas cooled to room temperature and benzyl bromide (1.7 mmol)was added to the solution. The reaction mixture was stirred andheated at 75 C for 48 h. After cooling the mixture, silica gel wasadded to the crude mixture, the solvent was evaporated underreduced pressure and the residue was purified by flash chromatography with a mixture of hexanes/EtOAc/TEA (95:5:1).

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 5433 - 5451

50
benzyl 2,3-O-isopropylidene-aldehydo-β-L-ribo-pentodialdo-1,4-furanoside N-tert-butanesulfinylimine [ No CAS ]
[ 130365-87-6 ]
benzyl (5R,S_R)-5-tert-butanesulfinamido-5-deoxy-5-C-[2-(4-trifluoromethylphenyl)ethyl]-2,3-O-isopropylidene-β-L-ribofuranoside [ No CAS ]

Reference： [1]ChemMedChem,2016,vol. 11,p. 133 - 141

51
[ 38841-98-4 ]
[ 130365-87-6 ]
C₁₇H₂₅F₃ [ No CAS ]

Reference： [1]ACS Catalysis,2016,vol. 6,p. 258 - 261

52
(6aR,9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-3-(phenylamino)-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(1H)-one [ No CAS ]
[ 130365-87-6 ]
[ 1160521-47-0 ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1149 - 1164

53
tert-butyl (S,Z)-(((tert-butoxycarbonyl)amino)(2-(3-(6-hydroxynaphthalen-2-yl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methylene)carbamate [ No CAS ]
[ 130365-87-6 ]
tert-butyl (S,Z)-(((tert-butoxycarbonyl)amino)(2-(3-(6-(4-(trifluoromethyl)phenethoxy)naphthalen-2-yl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methylene)carbamate [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 229 - 234

54
[ 603-35-0 ]
[ 130365-87-6 ]
[ 957565-37-6 ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 16210 - 16221
[2]Chemical Communications,2016,vol. 52,p. 7138 - 7141

55
[ 130365-87-6 ]
C₁₆H₁₂F₃NO₂ [ No CAS ]

Reference： [1]Chemical Communications,2016,vol. 52,p. 7138 - 7141

56
[ 130365-87-6 ]
C₁₆H₁₂F₃NO₂ [ No CAS ]

Reference： [1]Chemical Communications,2016,vol. 52,p. 7138 - 7141

57
[ 130365-87-6 ]
2-(3-(4-methoxyphenyl)prop-1-en-1-yl)-5-(trifluoromethyl)aniline [ No CAS ]

Reference： [1]Chemical Communications,2016,vol. 52,p. 7138 - 7141

58
[ 402-50-6 ]
[ 130365-87-6 ]

Reference： [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5622 - 5626

59
[ 261356-87-0 ]
[ 130365-87-6 ]
6-methyl-5-(propan-2-yl)-1-(4-trifluoromethylphenyl)heptan-3-ol [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 3014 - 3017

60
[ 130365-87-6 ]
C₁₈H₂₆F₃NO₃S [ No CAS ]
C₁₈H₂₆F₃NO₃S [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 3014 - 3017

61
[ 130365-87-6 ]
C₁₈H₂₈F₃NO₃S [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 3014 - 3017

62
[ 130365-87-6 ]
C₂₁H₂₂F₅N₅ [ No CAS ]

Reference： [1]Patent: WO2016/126869,2016,A1

63
[ 130365-87-6 ]
(±)-N-benzyl-3,3-difluoro-1-(4-(trifluoromethyl)phenethyl)piperidin-4-amine [ No CAS ]

Reference： [1]Patent: WO2016/126869,2016,A1

64
[ 130365-87-6 ]
(±)-N-benzyl-3,3-difluoro-N-methyl-1-(4-(trifluoromethyl)phenethyl)piperidin-4-amine [ No CAS ]

Reference： [1]Patent: WO2016/126869,2016,A1

65
[ 130365-87-6 ]
(±)-3,3-difluoro-N-methyl-1-(4-(trifluoromethyl)phenethyl)piperidin-4-amine [ No CAS ]

Reference： [1]Patent: WO2016/126869,2016,A1

66
[ 130365-87-6 ]
(±)-N-(3,3-difluoro-1-(4-(trifluoromethyl)phenethyl)piperidin-4-yl)-N-methyl-1-(tetra hydro-2H-pyran-2-yl)-1H-pyrazolo-[3,4-d]pyrimidin-4-amine [ No CAS ]

Reference： [1]Patent: WO2016/126869,2016,A1

67
3,3-difluoropiperidine-4,4-diol [ No CAS ]
[ 130365-87-6 ]
(±)-3,3-difluoro-1-(4-(trifluoromethyl)phenethyl)piperidine-4,4-diol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 110℃; for 0.5h;	[0186] To a stirred mixture of <strong>[130365-87-6]1-(2-bromoethyl)-4-(trifluoromethyl)benzene</strong> (1.0 g, 4.0 mmol)and 3,3-difluoropiperidine-4,4-diol (500 mg, 3.3 mmol) in n-BuOH was added DIPEA (1.3 mL,7.9 mmol). The mixture was heated to 110 C and stirred for 30 mm. The mixture wasconcentrated under vacuum, and purified by column chromatography over silica gel(hexane/ethyl acetate = 1/1) to afford the title product as a an oil (380 mg, 35%). 1H NMR(400 MHz, CDCI3) 6 7.55 (t, J = 8.4 Hz, 2H), 7.32 (t, J = 8.4 Hz, 2H), 3.12-3.04 (m, 1H), 2.94-2.80 (m, 5H), 2.77-2.63 (m, 3H), 2.01-1.96 (m, 1H).

Reference： [1]Patent: WO2016/126869,2016,A1 .Location in patent: Paragraph 0186

68
(±)-N-(3,3-difluoropiperidin-4-yl)-3-methyl-1H-pyrazolo-[3,4-d]pyrimidin-4-amine dihydrochloride [ No CAS ]
[ 130365-87-6 ]
(±)-N-(3,3-difluoro-1-(4-(trifluoromethyl)phenethyl)piperidin-4-yl)-3-methyl-1H-pyrazolo-[3,4-d]pyrimidin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
105 mg	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 120℃;	[0207] A mixture of <strong>[130365-87-6]1-(2-bromoethyl)-4-(trifluoromethyl)benzene</strong> (380 mg, 1.5 mmol), (±)-N(3,3-difluoropiperidin-4-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride (230 mg, 0.7 mmol) and DIPEA (0.6 mL, 3.44 mmol) in n-BuOH (4 mL) was heated to 120C. After stirring overnight at 120C, the mixture was concentrated. The concentrate was purified by column chromatography over silica gel (DCM/MeOH = 20/1) to afford the title compound as a gray powder (105 mg, 34%). MS (ESl) calcd for C20H21F5N6:440.2; found:441.4[M+H]. 1H NMR (400 MHz, CD3OD) 6 8.26 (s, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 5.02-4.91 (m, 1H), 3.41-3.35 (m, 1H), 3.11-3.09 (m, 1H), 2.97-2.91 (m, 2H), 2.84-2.76 (m, 2H), 2.68 (s, 3H), 2.62-2.52 (m, 1H), 2.46-2.40 (m, 1H), 2.11-1.98 (m, 2H).

Reference： [1]Patent: WO2016/126869,2016,A1 .Location in patent: Paragraph 0207

69
(1S,5S)-(+)-5-(3-methoxyphenyl)-9-oxo-2-azabicyclo[3.3.1]nonane [ No CAS ]
[ 130365-87-6 ]
(1S,5S)-(-)-5-(3-methoxyphenyl)-2-(4-(trifluoromethyl)phenethyl)-2-azabicyclo[3.3.1]nonan-9-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate; In acetonitrile; at 80℃; for 16h;	General procedure: To a solution of 1S,5S-2 or 1R,5R-2 (490 mg,2.0 mmol, 1 equiv) in anhydrous CH3CN (5 mL) was added K2CO3(550 mg, 4.0 mmol, 2.0 equiv) and alkyl bromide (3.0 mmol,1.5 equiv), respectively. The reaction was stirred at 80 C for 16 h.After cooling to room temperature, the solid was filtered off andthe solvent was evaporated. The residue was purified by flash columnchromatography eluting with hexane/EtOAc.