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[ CAS No. 34328-46-6 ]

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Chemical Structure| 34328-46-6

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Quality Control of [ 34328-46-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 34328-46-6 ]

Product Details of [ 34328-46-6 ]

CAS No. :	34328-46-6	MDL No. :	MFCD00040722
Formula :	C₈H₄ClF₃O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NIHMMULLFBKTOK-UHFFFAOYSA-N
M.W :	208.57	Pubchem ID :	118642
Synonyms :

Calculated chemistry of [ 34328-46-6 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	41.84
TPSA :	17.07 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.0 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.74
Log Po/w (XLOGP3) :	3.62
Log Po/w (WLOGP) :	4.32
Log Po/w (MLOGP) :	3.08
Log Po/w (SILICOS-IT) :	3.65
Consensus Log Po/w :	3.28

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.62
Solubility :	0.0497 mg/ml ; 0.000238 mol/l
Class :	Soluble
Log S (Ali) :	-3.67
Solubility :	0.045 mg/ml ; 0.000216 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.85
Solubility :	0.0291 mg/ml ; 0.00014 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	1.37

Safety of [ 34328-46-6 ]

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

Application In Synthesis of [ 34328-46-6 ]

* 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 [ 34328-46-6 ]
Downstream synthetic route of [ 34328-46-6 ]

[ 34328-46-6 ] Synthesis Path-Upstream 1~4

1
[ 144155-72-6 ]
[ 34328-46-6 ]

Reference： [1] Journal of Medicinal Chemistry, 1992, vol. 35, # 19, p. 3429 - 3447

2
[ 445-01-2 ]
[ 34328-46-6 ]

Reference： [1] Journal of Medicinal Chemistry, 1992, vol. 35, # 19, p. 3429 - 3447

3
[ 75-17-2 ]
[ 320-51-4 ]
[ 34328-46-6 ]

Reference： [1] Journal of Medicinal Chemistry, 1971, vol. 14, p. 862 - 866

4
[ 34328-46-6 ]
[ 7732-18-5 ]
[ 65735-71-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium borohydrid In methanol; chloroform	A. 4-Chloro-3-trifluoromethylbenzyl alcohol A 57 g (0.27 mole) portion of 4-chloro-3-trifluoromethylbenzadehyde in 400 ml of methanol was treated with 9 g (0.24 mole) of sodium borohydride at 0°-10° over 0.3 hr. The reaction mixture was stirred at room temperature for 3.5 hrs and filtered. The filtrate was concentrated under reduced pressure to give a solid residue which was partitioned between 250 ml of H₂ O and 250 ml of chloroform. The aqueous phase was again extracted with 250 ml of chloroform. The chloroform extracts were combined, washed with 100 ml of 10percent hydrochloric acid, 100 ml of H₂ O, dried over MgSO₄ and filtered. The filtrate was concentrated under reduced pressure to give 49 g (86percent) of a brown-orange liquid which crystallized upon cooling, m.p. 26°-29°.

Reference： [1] Patent: US4063022, 1977, A,

[ 34328-46-6 ] Synthesis Path-Downstream 1~68

1
[ 402-43-7 ]
[ 34328-46-6 ]
[ 34328-40-0 ]

Reference： [1]Journal of Medicinal Chemistry,1971,vol. 14,p. 862 - 866

2
[ 75-17-2 ]
[ 320-51-4 ]
[ 34328-46-6 ]

Reference： [1]Journal of Medicinal Chemistry,1971,vol. 14,p. 862 - 866

3
[ 107-10-8 ]
[ 34328-46-6 ]
[1-(4-Chloro-3-trifluoromethyl-phenyl)-meth-(E)-ylidene]-propyl-amine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1111 - 1118

4
[ 2537-48-6 ]
[ 34328-46-6 ]
[ 132604-91-2 ]
[ 132605-01-7 ]

Reference： [1]European Journal of Medicinal Chemistry,1990,vol. 25,p. 641 - 652
[2]European Journal of Medicinal Chemistry,1990,vol. 25,p. 641 - 652

5
[ 34328-46-6 ]
[ 75-04-7 ]
[1-(4-Chloro-3-trifluoromethyl-phenyl)-meth-(E)-ylidene]-ethyl-amine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1111 - 1118

6
[ 144155-72-6 ]
[ 34328-46-6 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 3429 - 3447

7
[ 34328-46-6 ]
[ 109-73-9 ]
Butyl-[1-(4-chloro-3-trifluoromethyl-phenyl)-meth-(E)-ylidene]-amine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1111 - 1118

8
[ 34328-46-6 ]
[ 74-89-5 ]
[1-(4-Chloro-3-trifluoromethyl-phenyl)-meth-(E)-ylidene]-methyl-amine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1111 - 1118

9
[ 34328-46-6 ]
[ 1439-36-7 ]
(E)-4-(4-Chloro-3-trifluoromethyl-phenyl)-but-3-en-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 3429 - 3447

10
[ 34328-46-6 ]
1-[(2S,5S)-5-(4-Chloro-phenoxymethyl)-2-(4-chloro-3-trifluoromethyl-phenyl)-oxazolidin-3-yl]-ethanone [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 4556 - 4566

11
[ 34328-46-6 ]
1-[(2S,5R)-5-(4-Chloro-phenoxymethyl)-2-(4-chloro-3-trifluoromethyl-phenyl)-oxazolidin-3-yl]-ethanone [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 4556 - 4566

12
[ 34328-46-6 ]
2-[2-(4-Chloro-3-trifluoromethyl-phenyl)-ethyl]-6-hydroxy-benzoic acid [ No CAS ]

Reference： [1]Bioscience, Biotechnology and Biochemistry,1996,vol. 60,p. 862 - 865

13
[ 34328-46-6 ]
2-[2-(4-Chloro-3-trifluoromethyl-phenyl)-ethyl]-6-methoxy-benzoic acid [ No CAS ]

Reference： [1]Bioscience, Biotechnology and Biochemistry,1996,vol. 60,p. 862 - 865

14
[ 34328-46-6 ]
2-[2-(4-Chloro-3-trifluoromethyl-phenyl)-ethyl]-6-methoxy-benzoic acid ethyl ester [ No CAS ]

Reference： [1]Bioscience, Biotechnology and Biochemistry,1996,vol. 60,p. 862 - 865

15
[ 445-01-2 ]
[ 34328-46-6 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 3429 - 3447

16
[ 34328-46-6 ]
[ 144128-81-4 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 3429 - 3447

17
[ 34328-46-6 ]
[ 144155-23-7 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 3429 - 3447

18
[ 34328-46-6 ]
[ 144155-52-2 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 3429 - 3447

19
[ 34328-46-6 ]
C₁₄H₈ClF₃O₄^(2-)*2Na⁽¹⁺⁾ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 3429 - 3447

20
[ 34328-46-6 ]
[ 144155-81-7 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 3429 - 3447

21
[ 34328-46-6 ]
[ 90390-42-4 ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1111 - 1118

22
[ 34328-46-6 ]
[ 90390-43-5 ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1111 - 1118

23
[ 34328-46-6 ]
[ 90390-44-6 ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1111 - 1118

24
[ 34328-46-6 ]
[ 90390-45-7 ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1111 - 1118

25
[ 34328-46-6 ]
[ 348-84-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With methylmagnesium chloride; In tetrahydrofuran; diethyl ether; at -78 - -20℃;	[4-CHLORO-3- (TRIFLUOROMETHYL)] benzylaldhyde (3.0 g, 14.4 mmol) in diethyl ether was cooled [TO-78 C. METHYLMAGNESIUM] chloride (3. 0M solution in THF, 29 mmol) was added dropwise. The reaction was warmed up slowly [TO-20] C. TLC showed the reaction was complete. It was quenched with saturated amonium chloride solution. The aqueous layer was extracted with ethyl acetate, organic layer wre combined and washed with water, brine, and dried with magnesium sulfate. This gave [1- (4-CHLORO-3-TRIFLUOROMETHYLPHENYL)] ethanol (3.2g, [99%)] after the solvent was removed under reduced pressure. [1- (4-CHLORO-4-TRIFLUOROMETHYL-] phenyl) ethanol was then oxidized by [SWERN] oxidation (2.5 eq. DMSO, 1.2 eq. oxyal chloride, 5 eq. triethylamine, [60ML] of [DICHLOROMETHANE,-78] C). The resulting 1- (3-chloro-4- trifluoromethylphenyl) ethanone (3 g, 95% yield) was brominated according to a literature [PROCEDURE (HORNG-CHIH, HUANG ET AL. , J. MED. CHEM. ; 1996, VOL. 39,253-266). 4-CHLORO-3- (TRIFLUOROMETHYL) -PHENACYL BROMIDE WAS OBTAINED IN 70% YIELD. LC/MS (ES+) M/E 303 [M+1]]

Reference： [1]Patent: WO2003/101970,2003,A1 .Location in patent: Page 10-11

26
[ 34328-46-6 ]
[ 38622-91-2 ]
[ 741290-07-3 ]

Yield	Reaction Conditions	Operation in experiment
		To a round-bottom flask containing <strong>[34328-46-6]4-chloro-3-(trifluoromethyl)benzaldehyde</strong> (1.83 g, 8.8 mmol, 1.1 eq) and tosylmethyl isocyanide (1.56 g, 8.0 mmol, 1.0 eq) was added EtOH (15 mL, absolute) and cat. KCN (48 mg, 0.80 mmol, 10 mol %). The mixture was stirred at room temperature (rt) for 3 h and the resulting suspension was filtered. The solid residue was washed with cold EtOH and dried in vacuo. The tosyloxazoline intermediate was added to a glass pressure vessel containing NH3 in methanol (50 ml of a 7.0 N solution). The vessel was capped and heated to 100 C. for 14 h. The contents were carefully cooled to 0 C. and the vessel was opened. Upon warming slowly to rt, most of the ammonia had dissipated. The mixture was transferred to a round-bottom flask and concentrated in vacuo. 2-(6-Cyclohexyloxymethyl-2-imidazol-1-yl-pyrimidin-4-ylamino)-4-methyl-pentanoic acid (3-ethoxy-propyl)-amide (312) (0.334 g, 17%) was isolated from the crude mixture by flash chromatography (dichloromethane/methanol 10/1). ESI-MS (m/z) 247 [M+H]+.

Reference： [1]Patent: US2004/87601,2004,A1 .Location in patent: Page 18

27
potassium cyanide [ No CAS ]
[ 34328-46-6 ]
p-tolylsulfonyl isocyanide [ No CAS ]
C₁₇H₁₃ClF₃NO₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 20℃; for 3h;	To a round-bottom flask containing 4-CHLORO-3- (TRIFLUOROMETHYL) benzaldehyde (1.83 gram) and TosMIC (1.56 gram) was added EtOH (15 mL, absolute) and KCN (48 mg) The mixture was stirred at room temperature for 3 hours and the resulting suspension was filtered. The solid residue was washed with cold EtOH and dried in vacuo. The tosyloxazoline intermediate was added to a glass pressure vessel containing NH3 in methanol (50 ML of a 7.0 N solution). The vessel was capped and HEATED TO 100 C for 14 hours. The contents were carefully cooled to 0 C and the vessel was opened. Upon warming slowly to room temperature, most of the ammonia had dissipated. The mixture was transferred to a round-bottom flask and concentrated in vacuo. The title compound (0.334 g, 17%) was isolated from the crude mixture by flash chromatography (DICHLOROMETHANE/METHANOL 10/1). ESI-MS (MILZ) 247 [M+H] +.

Reference： [1]Patent: WO2004/69829,2004,A1 .Location in patent: Page 16-17

28
[ 773071-16-2 ]
[ 34328-46-6 ]
2-(3-{6-Chloro-3-[(4-chloro-3-trifluoromethylbenzylidene)-amino]-4-oxo-3,4-dihydro-quinazolin-2-yl}-benzylsulfanyl)-ethanesulfonic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	In toluene; at 20℃; for 12h;Heating / reflux;	2-[3-(3-Amino-6-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-benzylsulfanyl]-ethanesulfonic acid (50.0 mg) was dissolved in anhydrous toluene (1.0 ml). Subsequently, <strong>[34328-46-6]4-chloro-3-trifluoromethylbenzaldehyde</strong> (compound C) (50.0 mul) was added to the solution at room temperature, and the mixture was heated under reflux with stirring for 12 hr. After the completion of the reaction, the reaction solution was allowed to cool at room temperature, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography on silica gel, followed by drying through a vacuum pump to give the title compound 703 (32.0 mg, yield 44.0%). 1H-NMR (CDCl3, 400 MHz): delta 9.16 (1H, s), 8.15 - 8.25 (1H, m), 7.38 - 7.90 (9H, m), 3.84 (2H, s), 2.97 - 3.05 (2H, m), 2.80 - 2.87 (2H, m) Mass spectrometric value (ESI-MS) 614, 616 (M-1)

Reference： [1]Patent: EP1614676,2006,A1 .Location in patent: Page/Page column 134

29
[ 773071-17-3 ]
[ 34328-46-6 ]
2-{3-[4-chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	In toluene; at 20℃; for 12h;Heating / reflux;	2-[3-(4-Chloro-2-hydrazinocarbonyl-phenylcarbamoyl)-benzylsulfanyl]-ethanesulfonic acid (50.0 mg) was dissolved in anhydrous toluene (1.0 ml). Subsequently, <strong>[34328-46-6]4-chloro-3-trifluoromethylbenzaldehyde</strong> (compound C) (50.0 mul) was added to the solution at room temperature, and the mixture was heated under reflux with stirring for 12 hr. After the completion of the reaction, the reaction solution was allowed to cool at room temperature, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography on silica gel and was dried through a vacuum pump to give the title compound 709 (47.2 mg, yield 56.0%). 1H-NMR (CD3OD, 400 MHz): delta 8.52 (1H, d, J = 9.0 Hz), 7.38 - 8.40 (10H, m), 3.89 (2H, s), 2.94 - 3.06 (2H, m), 2.70 - 2.88 (2H, m) Mass spectrometric value (ESI-MS) 632 (M-1)

Reference： [1]Patent: EP1614676,2006,A1 .Location in patent: Page/Page column 136

30
[ 773071-34-4 ]
[ 34328-46-6 ]
N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-dipropylamino-phenyl]-3-[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	In toluene; at 20℃; for 15h;	3-[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-(4-dipropylamino-2-hydrazinocarbonyl-phenyl)-benzamide (47 mg) as the hydrazine compound produced by the above reaction was dissolved in anhydrous toluene (1.0 ml). 3-Trifluoromethyl-4-chlorobenzaldehyde (compound C) (40 mul) was added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, the reaction product was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 911 (57 mg, yield 88%). 1H-NMR (CDCl3, 400 MHz): delta 0.78 (6H, t, J = 7.1 Hz), 1.04 (6H, t, J = 7.1 Hz), 1.37 (4H, m), 2.26 (3H, s), 2.50 - 2.75 (8H, m), 2.85 (4H, m), 3.62 (2H, s), 6.49 (1H, d, J = 7.8 Hz), 6.65 (1H, s), 7.44 (1H, dd, J = 7.6 Hz, J = 7.6 Hz), 7.55 (2H, m), 7.80 - 8.15 (5H, m), 8.63 (1H, s), 10.83 (1H, s) Mass spectrometric value (ESI-MS) 685 (M-1)

Reference： [1]Patent: EP1614676,2006,A1 .Location in patent: Page/Page column 171-172

31
[ 773071-44-6 ]
[ 34328-46-6 ]
3-[bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	acetic acid; In toluene; at 20 - 90℃; for 3h;	3-[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-(2-hydrazino-carbonyl-4-piperidin-1-ylphenyl)benzamide (53 mg) produced by the above process was dissolved in anhydrous toluene (5 ml). 4-Chloro-3-(trifluoromethyl)benzaldehyde (compound C) (69 mg) and a catalytic amount of acetic acid were added dropwise to the solution at room temperature, and the mixture was then stirred at 90C for 3 hr. After the completion of the reaction, the reaction solution was allowed to stand for cooling, and the resultant crystals were collected by Kiriyama Rohto to give the title compound 942 (15 mg, yield 20%). The filtrate obtained by the filtration through Kiriyama Rohto was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to again give the title compound 942 (37 mg, yield 50%) (final step: total yield 70%). 1H-NMR (CD3OD, 400 MHz): delta 8.31 - 8.38 (3H, m), 8.00 - 8.07 (2H, m), 7.86 (1H, d, J = 8.0 Hz), 7.67 (1H, d, J = 8.6 Hz), 7.58 (1H, d, J = 7.8 Hz), 7.48 (1H, dd, J = 7.6 Hz, J = 7.6 Hz), 7.38 (1H, d, J = 2.7 Hz), 7.23 (1H, dd, J = 2.7 Hz, J = 9.0 Hz), 3.83 - 3.95 (4H, m), 3.20 - 3.25 (4H, m), 2.38 - 2.55 (4H, m), 1.70 - 1.78 (4H, m), 1.58 - 1.66 (2H, m), 1.07 (3H, s), 1.06 (3H, s) Mass spectrometric value (ESI-MS) 672, 674 (M-1)

Reference： [1]Patent: EP1614676,2006,A1 .Location in patent: Page/Page column 179

32
[ 773071-65-1 ]
[ 34328-46-6 ]
N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-5-piperidin-1-ylmethyl-thiophen-2-yl]-3-diethylaminomethyl-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	acetic acid; In toluene; at 20℃; for 3h;	Subsequently, 3-diethylaminomethyl-N-(3-hydrazinocarbonyl-4-methyl-5-piperidin-1-ylmethylthiophen-2-yl)-benzamide (15 mg) produced by the above process was dissolved in anhydrous toluene. 4-Chloro-3-(trifluoromethyl)benzaldehyde (compound C) (21 mg: dissolved in 1 ml of anhydrous toluene) and a catalytic amount of acetic acid were added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 3 hr. After the completion of the reaction, the reaction solution was neutralized with a saturated sodium hydrogencarbonate solution, and was then subjected to separatory extraction with ethyl acetate, and the organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 956 (6.0 mg, yield 29%). 1H-NMR (CDCL3, 400 MHz): delta 8.26 (1H, bs), 8.05 (1H, s), 8.00 (1H, s), 7.95 (1H, d, J = 8.0 Hz), 7.88 (1H, d, J = 7.6 Hz), 7.55 - 7.62 (2H, m), 7.42 - 7.48 (1H, m), 3.67 (2H, s), 2.48 - 2.60 (10H, m), 1.24 - 2.00 (9H, m), 1.07 (6H, t, J = 7.1 Hz) Mass spectrometric value (ESI-MS) 646 (M-1)

Reference： [1]Patent: EP1614676,2006,A1 .Location in patent: Page/Page column 185

33
[ 773071-61-7 ]
[ 34328-46-6 ]
N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-5-methyl-thiophen-2-yl]-3,4-dimethoxy-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	acetic acid; In toluene; at 20℃; for 3h;	Subsequently, N-(3-hydrazinocarbonyl)-5-methylthiophen-2-yl)-3, 4-dimethoxy-benzamide (8.0 mg) was dissolved in anhydrous toluene (5 ml), <strong>[34328-46-6]4-chloro-3-(trifluoromethyl)benzaldehyde</strong> (compound C) (15 mg: dissolved in 1 ml of anhydrous toluene) and a catalytic amount of acetic acid were added dropwise to the solution at room temperature, and the mixture was stirred at that temperature for 3 hr. After the completion of the reaction, the reaction solution was neutralized with a saturated sodium hydrogencarbonate solution and was then subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 955 (5.0 mg, yield 38%). 1H-NMR (CDCL3, 400 MHz): delta 12.66 (1H, bs), 9.19 (1H, bs), 8.19 (1H, bs), 8.02 (1H, s), 7.80 - 7.92 (1H, m), 7.62 - 7.65 (2H, m), 7.56 (1H, d, J = 8.3 Hz), 6.92 (1H, d, J = 8.8 Hz), 3.97 (3H, s), 3.95 (3H, s), 2.44 (3H, s) Mass spectrometric value (ESI-MS) 524 (M-1)

Reference： [1]Patent: EP1614676,2006,A1 .Location in patent: Page/Page column 184

34
2-(3-aminoprop-1-ylamino)-1H-quinolin-4-one dihydrochloride [ No CAS ]
[ 34328-46-6 ]
2-[3-(4-Chloro-3-trifluoromethylbenzylamino)prop-1-ylamino]-1H-quinolin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium methylate; In methanol; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran;	Example 38 2-[3-(4-Chloro-3-trifluoromethylbenzylamino)prop-1-ylamino]-1H-quinolin-4-one compound from Example 1(b) (73 mg, 0.25 mmol) in methanol (6 ml) was added AcOH (0.12 ml) and NaOMe (1.0 ml, 0.5 M in MeOH), followed by <strong>[34328-46-6]4-chloro-3-trifluoromethylbenzaldehyde</strong> (52 mg, 0.25 mmol). After stirring under argon for 25 min NaCNBH3 (24 mg, 0.38 mmol) was added. The reaction was worked up as in Example 34 to give a colourless gum which was further purified by flash chromatography on silica gel eluding with 10% (9:1 MeOH/NH3) in DCM to give the title compound as a colourless gum (73 mg, 71%); deltaH (CD3OD) 1.82-1.93 (2H, m), 2.71 (2H, t), 3.38 (2H, t), 3.84 (2H, s), 5.65 (1H, s), 7.20-7.35 (2H, m), 7.47-7.62 (3H, m), 7.90 (1H, s), 8.08 (1H, d); MS (ES+) 410 (27% MH+), 201 (100).

Reference： [1]Patent: US6320051,2001,B1

35
[ 34328-46-6 ]
[ 103680-62-2 ]
1,3-(4-chloro-3-trifluoromethylbenzylamino)propyl(diethoxymethyl)phosphinic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		PREPARATION EXAMPLE 14 In a manner analogous to that described in Preparation Example 1,3-(4-chloro-3-trifluoromethylbenzylamino)propyl(diethoxymethyl)phosphinic acid having a melting point of 138-139 can be prepared starting from 3-aminopropyl(diethoxymethyl)phosphinic acid ethyl ester and <strong>[34328-46-6]4-chloro-3-trifluoromethylbenzaldehyde</strong>.

Reference： [1]Patent: US5229379,1993,A

36
[ 2537-48-6 ]
[ 34328-46-6 ]
[ 132605-01-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In tetrahydrofuran;	The compounds of the formula (II) listed in Table 6 below can be prepared analogously. Example for the preparation of the substituted cinnamonitriles employed as precursors (cf., for example, Foucaud et al. Synthesis (1979), p. 884 to 885): STR37 A solution of 10.6 g (0.06 mol) of diethyl cyanomethylphosphonate and 12.5 g (0.06 mol) of 4-chloro-3trifluoromethyl-benzaldehyde in 65 ml of tetrahydrofuran is added dropwise to a suspension of 6.7 g (0.12 mol) of pulverulent potassium hydroxide in 185 ml of tetrahydrofuran. During this process the temperature of the reaction mixture rises slightly. Stirring is subsequently continued at room temperature for 20 minutes, and the solid which separates out in this process is filtered off and washed with tetrahydrofuran. The filtrate is concentrated in vacuo and the residue which remains is dried. 12.1 g (87.0% of theory) of 4-chloro-3-trifluoromethyl-cinnamonitrile are obtained in the form of an E/Z isomer mixture. M.p.: 89-92 C. 1 H NMR (CDCl3, delta): 5.60; 7.13 (2d, =CH, JH,H =12 Hz; Z form); 5.96; 7.38 (2d, =CH, JH,H =16.5 Hz; E form); 7.57-8.07 (m, arom.) ppm
	With potassium hydroxide; In tetrahydrofuran;	The compounds of the formula (II) listed in Table 7 below may be prepared in an analogous manner. Example of the preparation of the cinnamonitriles employed as precursors (cf., e.g., Foucaud et al. Synthesis (1979), pp. 884 to 885): STR45 A solution consisting of 10.6 g (0.06 mol) of diethyl cyanomethylphosphonate and 12.5 g (0.06 mol) of <strong>[34328-46-6]4-chloro-3-trifluoromethylbenzaldehyde</strong> in 65 ml of tetrahydrofuran is added dropwise to a suspension of 6.7 g (0.12 mol) of powdered potassium hydroxide in 185 ml of tetrahydrofuran. During this process, there is a slight evolution of heat. Subsequently, the mixture is stirred at room temperature for 20 minutes and the solid material which separates off is filtered off and washed with tetrahydrofuran. The filtrate is concentrated in vacuo and the remaining residue is dried. 12.1 g (87.0% of theory) of 4-chloro-3-trifluoromethyl-cinnamonitrile are obtained as an E/Z isomeric mixture. M.p.: 89-92 C. 1 H NMR (CDCl3, delta): 5.60; 7.13 (2d, =CH, JH,H =12 Hz; Z form); 5.96; 7.38 (2d, =CH, JH,H =16.5 Hz; E form); 7.57-8.07 (m, arom.) ppm

Reference： [1]Patent: US5371231,1994,A
[2]Patent: US5428049,1995,A

37
[ 34328-46-6 ]
[ 7732-18-5 ]
[ 65735-71-9 ]

Yield	Reaction Conditions	Operation in experiment
49 g (86%)	With sodium borohydrid; In methanol; chloroform;	A. 4-Chloro-3-trifluoromethylbenzyl alcohol A 57 g (0.27 mole) portion of 4-chloro-3-trifluoromethylbenzadehyde in 400 ml of methanol was treated with 9 g (0.24 mole) of sodium borohydride at 0°-10° over 0.3 hr. The reaction mixture was stirred at room temperature for 3.5 hrs and filtered. The filtrate was concentrated under reduced pressure to give a solid residue which was partitioned between 250 ml of H2 O and 250 ml of chloroform. The aqueous phase was again extracted with 250 ml of chloroform. The chloroform extracts were combined, washed with 100 ml of 10percent hydrochloric acid, 100 ml of H2 O, dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to give 49 g (86percent) of a brown-orange liquid which crystallized upon cooling, m.p. 26°-29°.

Reference： [1]Patent: US4063022,1977,A

38
[ 104-03-0 ]
[ 34328-46-6 ]
[ 67-63-0 ]
[ 313677-00-8 ]

Yield	Reaction Conditions	Operation in experiment
	In piperidine;	Step A (Scheme 1): Preparation of trans-1-Chloro-2-trifluoromethyl-4-[2-(4-nitrophenyl)ethenyl]benzene A mixture of p-nitrophenylacetic acid (51.85 g, 0.29 mol) and <strong>[34328-46-6]4-chloro-3-trifluoromethylbenzaldehyde</strong> (47.85 g, 0.23 mol) in piperidine (19.5 g, 0.23 mol) was heated under N2 atmosphere to 150 C. to 160 C. for 1 hour. The reaction mixture was cooled to 80 C. to 100 C. and refluxing i-PrOH (150 mL) was added. The mixture was continued to cool to room temperature and then placed under refrigeration for 5 hours. The crystalline precipitate was filtered off, rinsed with cold i-PrOH, and dried at room temperature in a vacuum oven overnight to yield trans-1-chloro-2-trifluoromethyl-4-[2-(4-nitrophenyl)ethenyl]benzene as an orange solid, 22.53 g (68.75 mmol, 30%). mp 173-174 C. MS: 327.0 (M+)

Reference： [1]Patent: US2004/220235,2004,A1

39
[ 104-03-0 ]
[ 34328-46-6 ]
[ 1130849-43-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 654 - 657

40
[ 34328-46-6 ]
[ 20349-86-4 ]
methyl 2-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxy-2H-chromene-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	piperidine; acetic acid; In isopropyl alcohol; for 16.5h;Reflux;	EXAMPLE 2-1; Preparation of racemic 2-(4-chloro-3-(trifluoromethyl)phenyl)-2H-chromene-3- carboxylic acid; [00128] Step 1. A mixture of methyl 3-(2-hydroxyphenyl)-3-oxopropanoate (prepared according to Cushman, M. et al., J. Med. Chem. 1991, 200 mg, 1.03 mmol) and <strong>[34328-46-6]4-chloro-3-(trifluoromethyl)benzaldehyde</strong> (148 muL, 1.03 mmol) in isopropanol (4.0 mL) was treated with piperidine (10 muL, 103 mumol) and acetic acid (5.9 muL, 103 mumol) and heated to reflux for 16.5 h. After this time, water (2.0 mL) was added and the solution was slowly cooled to rt, whereupon crystals formed. After standing at rt, the mixture was cooled on ice, and the resulting crystals were collected by filtration and dried to provide methyl 2-(4-chloro-3-(trifluoromethyl)phenyl)-4-oxochroman-3- carboxylate as a white crystalline solid (204 mg, 51%). A second crop (47 mg) was obtained from the mother liquor, raising the total yield to 63%. The NMR indicated predominantly the enolic form. 1H NMR (500 MHz, CDCl3) delta ppm 3.79 (s, 3 H) 6.24 (s, 1 H) 6.82 (d, J=8.2 Hz, 1 H) 7.00 (t, J=7.7 Hz, 1 H) 7.31 (t, J=6.9 Hz, 1 H) 7.42 (m, 2 H) 7.70 (m, 2 H) 12.27 (br. s, 1 H). Mass spectrum m/z 407.19, 409.18 (M+Na)+.

Reference： [1]Patent: WO2010/9069,2010,A1 .Location in patent: Page/Page column 36

41
[ 34328-46-6 ]
[ 75-16-1 ]
[ 348-84-5 ]

Yield	Reaction Conditions	Operation in experiment
62%		<strong>[34328-46-6]4-chloro-3-trifluoromethyl-benzaldehyde</strong> (6.19 g, 29.7 mmol) is dissolved in 124 mL of THF under a nitrogen atmosphere. The reaction medium is cooled to -78C before adding dropwise MeMgBr (13 mL, 3M / Et2O, 38.6 mmol) , and then stirred for a further 2 hours at this low temperature, and finally neutralized by adding 60 mL of a saturated NH4Cl solution. The reaction medium is extracted twice with ethyl acetate. The organic phases are combined, washed with a saturated NaCl solution, and then dried on magnesium sulfate, filtered and concentrated under reduced pressure. The thereby obtained residue is purified on a column of 120 g of silica (92 mL / min; gradient of 0% to 35% ethyl acetate in heptane in 40 min), in order to obtain the compound 149A (5.71 g, 62%) .HPLC: RT = 5.71 min, 98% (colonne XBridge)1H NMR, dmso-de, delta (ppm) : 1.33 (d, 3H); 4.81 (quintet, IH); 5.46 (d, IH, exch) ; 7.60-7.69 (m, 2H); 7.81 (s, IH) .

Reference： [1]Patent: WO2010/100139,2010,A1 .Location in patent: Page/Page column 102

42
[ 6629-04-5 ]
[ 34328-46-6 ]
[ 1253933-29-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2010,vol. 8,p. 4281 - 4288

43
[ 34328-46-6 ]
3-Trifluor-4-chlorbenzaldoxim [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a sealed vial was added <strong>[34328-46-6]4-chloro-3-trifluoromethyl-benzaldehyde</strong> (1 g, 4.79 mmol), hydroxylamine hydrochloride (666 mg, 9.59 mmol), potassium carbonate (1.3 g, 9.59 mmol), and EtOH (8 mL). The reaction was stirred for 4 hr at ambient temperature, then diluted with H2O and the pH adjusted to pH ~ 6-7 with 10% citric acid. The aqueous layer was then extracted with EtOAc, washed with H2O, dried over sodium sulfate and concentrated under reduced pressure. The resulting solid oxime was filtered, washed with Hexanes: CH2Cl2 (10:1) and used in the next step without further purification.

Reference： [1]Patent: WO2010/120741,2010,A1 .Location in patent: Page/Page column 33-34

44
[ 1694-31-1 ]
[ 34328-46-6 ]
2-[1-(4-Chloro-3-trifluoromethyl-phenyl)-meth-(Z)-ylidene]-3-oxo-butyric acid tert-butyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 6273 - 6276

45
[ 34328-46-6 ]
[ 1271302-14-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 892 - 901

46
[ 34328-46-6 ]
[ 1271302-21-6 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 892 - 901

47
[ 34328-46-6 ]
[ 124355-25-5 ]
C₃₇H₃₁ClF₃N₃O₄ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 892 - 901

48
[ 34328-46-6 ]
[ 1276115-61-7 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 2080 - 2094

49
[ 34328-46-6 ]
[ 78-96-6 ]
C₁₁H₁₁ClF₃NO [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 2080 - 2094

50
[ 695-34-1 ]
[ 826-81-3 ]
[ 34328-46-6 ]
[ 1314510-19-4 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 20℃; for 336h;	Preparation of AD4- 13021 :[0440 ] 2-Amino-4-picoline (1.08 g, 0.01 mol) and <strong>[34328-46-6]4-chloro-3-(trifluoromethyl)benzaldehyde</strong> (2.08 g, 0.01 mol) are weighed into a 100 ml roundbottom flask and stirred with 50 ml of absolute EtOH to dissolve. 8 -Hydroxy quinaldine (1.59 g, 0.01 mol) is added and the mixture stirred, at room temperature, for a few minutes until a clear yellowish solution is obtained. The reaction mixture is then capped with a plastic stopper and stirred, at room temperature, for 14 days. Tic (silica-gel, 2: 1 Hexanes/acetone) indicates some starting material remaining in addition to a major new spot slightly below the 8 -hydroxy quinaldine spot. The crude material is chromatographed on 500 ml flash silica-gel eluting with 2-25% acetone/hexanes. The elution solvent is as follows: 1 litre of 2% Acetone/hexanes; 1 litre of 3% acetone/hexanes; 1 litre of 5% acetone/hexanes; 1 liter of 7.5% acetone/hexanes; 1 litre of 10% acetone/hexanes; 1 litre of 15% acetone hexanes; 1 litre of 20% acetone/hexanes and 1 litre of 25% acetone/hexanes. 150 ml fractions are collected. Fractions 1-3 contain unreacted 8 -hydroxy quinaldine. Fractions 11-13, containing the product, are concentrated on a rotovap to give a light-green oil. The oil is dissolved in 200 ml hexanes with a few ml of acetone. The resulting solution is allowed to stand at room temperature overnight. 2.9 g of the product forms as an off white crystalline solid and is isolated by filtration. [0441 ] TLC:[0442 ] 2,3-Difluoro-4-methylbenzaldehyde Rf = 0.8[0443] 8 -Hydroxy quinaldine Rf = 0.7[0444 ] Product Rf = 0.55[0445] 2-Amino-4-picoline Rf = 0.2[0446] 8 -Hydroxy quinaldine and the product both glow bright yellow under long wavelength (366 nM) UV light and the product also glows bright yellow under the short wavelength (254 nM) UV light. After standing for several hours in the air tic spots from both 8- hydroxyquinaldine and the product turn yellow and then brown without any staining.

Reference： [1]Patent: WO2011/85126,A1 .Location in patent: Page/Page column 167-168
Patent: ,2011, .Location in patent: Page/Page column 167-168

51
[ 34328-46-6 ]
[ 1221962-33-9 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6714 - 6723

52
[ 34328-46-6 ]
[ 1221962-34-0 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6714 - 6723

53
[ 34328-46-6 ]
C₁₈H₁₅Cl₂F₃N₂O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6714 - 6723

54
[ 34328-46-6 ]
C₁₂H₁₀ClF₃O₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6714 - 6723

55
[ 34328-46-6 ]
[ 141-97-9 ]
C₂₀H₂₂ClF₃O₆ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6714 - 6723

56
[ 1136-86-3 ]
[ 34328-46-6 ]
[ 1442690-92-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium hydroxide; In methanol; at 20℃; for 24h;	General procedure: Reagents used were obtained commercially from Sigma-Aldrich. Type 1 and 2 chalcones were prepared by aldol condensation of acetophenones (1 mmol) with aldehydes (1 mmol), in methanol (15 mL), KOH (50% v/v), at room temperature with magnetic agitation for 24 h. The volume of KOH varied according to the different inductive and mesomeric effects for the various substituents of the aromatic rings: 2 mL for compounds 2a, 2b and 2c; 40 drops for compounds 2d and 3p; 15 drops for compounds 3d and 3q; 13 drops for compounds 3a, 3h, 3j and 3o; 10 drops for compounds 3b, 3c, 3e, 3f, 3i and 3k; 8 drops for compounds 3n, 3r and 3s; and 5 drops for compounds 3g, 3l and 3m. KOH addition was stopped at the first sign of precipitation. Distilled water and 10% hydrochloric acid were added to the reaction for total precipitation of the compounds, which were then obtained by vacuum filtration and later recrystallized in dichloromethane, with forced precipitation by hexane. The purity of the synthesized compounds was analyzed by thin-layer chromatography (TLC) using Merck silica pre-coated aluminum plates of 200 mm thickness, with several solvent systems of different polarities. Compounds were visualized with ultraviolet light (lambda = 254 and 360 nm) and using sulfuric anisaldehyde solution followed by heat application as the developing agent. The chalcones were soluble in dimethyl sulfoxide, acetone, acetyl acetate, chloroform and dichloromethane. Compounds 3a-3o and 3r were previously cited in the literature [6,7,16-21]. Chalcone derivatives 2a, 2b and 2c were previously synthesized by our group [13-15] and 2d, 3p, 3q and 3s are novel compounds.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 63,p. 501 - 510

57
[ 75-52-5 ]
[ 34328-46-6 ]
C₉H₅ClF₃NO₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 6248 - 6258

58
[ 34328-46-6 ]
[ 134074-38-7 ]
[ 79-11-8 ]
methyl (2Z)-2-[(4-chloro-3-trifluoromethanephenyl)methylidene]-5-(4-methoxyphenyl)-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate [ No CAS ]

Reference： [1]Medicinal Chemistry Research,2014,vol. 23,p. 168 - 180

59
[ 34328-46-6 ]
[ 134141-12-1 ]
[ 79-11-8 ]
methyl (2Z)-5-(4-bromophenyl)-2-[4-chloro-3-(trifluoromethyl)phenyl]methylidene}-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate [ No CAS ]

Reference： [1]Medicinal Chemistry Research,2014,vol. 23,p. 168 - 180

60
[ 34328-46-6 ]
[ 1587727-52-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydroxylamine; In tetrahydrofuran; methanol; ethanol; water;	Step 2: Synthesis of (E)-1-[4-chloro-3-(trifluoromethyl)phenyl]-N-hydroxymethanimine (C19) To a solution of <strong>[34328-46-6]4-chloro-3-(trifluoromethyl)benzaldehyde</strong> (93.9 mg, 0.45 mmol) in tetrahydrofuran (0.9 mL) and ethanol (0.9 mL) was added hydroxylamine (50% in water, 0.20 mL) and the reaction was maintained at room temperature for 36 hours. Methanol (3.0 mL) was added, the solvent was removed in vacuo, and the residue was triturated with toluene (2*1 mL) to afford the title compound as a solid. Yield: 101 mg, 0.45 mmol, 100%.

Reference： [1]Patent: US2014/88111,2014,A1 .Location in patent: Page/Page column

61
[ 34328-46-6 ]
4-chloro-N-hydroxy-3-(trifluoromethyl)benzenecarboximidoyl chloride [ No CAS ]

Reference： [1]Patent: US2014/88111,2014,A1

62
[ 540-88-5 ]
[ 34328-46-6 ]
[ 1612773-14-4 ]

Yield	Reaction Conditions	Operation in experiment
98%	With titanium tetrachloride; triethylamine; In dichloromethane; at 0 - 25℃;Inert atmosphere;	General procedure: To a mixture of an aldehyde (0.1 mol) and alkyl acetate (0.1 mol) in dichloromethane (15 mL) was added Et3N (0.3 mol). The resulting reaction mixture was cooled to 0 C under nitrogen atmosphere. To this was added TiCl4 (0.12 mol) dropwise over a period of 15 min and the mixture was stirred for further 2-4 h at room temperature. When the reaction was complete as confirmed by TLC, the mixture was diluted with water (25 mL) and the dichloromethane layer was separated. The organic phase was washed with 0.5 M aqueous HCl, water and brine. It was then dried over anhydrous Na2SO4 and evaporated under reduced pressure to afford the corresponding alkyl (E)-alpha,beta-unsaturated carboxylate (2) in excellent yield and purity.

Reference： [1]Tetrahedron Letters,2014,vol. 55,p. 3503 - 3506

63
[ 34328-46-6 ]
[ 1621586-86-4 ]

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 84,p. 160 - 172
[2]Journal of Enzyme Inhibition and Medicinal Chemistry,2016,vol. 31,p. 197 - 202

64
[ 34328-46-6 ]
4-(2-(4-chloro-3-(trifluoromethyl)phenyl)-4,5-dihydroimidazol-1-yl)benzenesulfonamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 84,p. 160 - 172
[2]Journal of Enzyme Inhibition and Medicinal Chemistry,2016,vol. 31,p. 197 - 202

65
[ 34328-46-6 ]
[ 1621586-71-7 ]

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 84,p. 160 - 172

66
[ 34328-46-6 ]
[ 107-15-3 ]
[ 1621586-59-1 ]

Yield	Reaction Conditions	Operation in experiment
53%		General procedure: Ethylenediamine (10.5mmol) was added to a stirred solution of aldehyde (10.0mmol) in CH2Cl2 (50mL) at 0C, and the resulting solution was stirred for 20min. N-bromosuccinimide (10.5mmol) was then added in portions over 10min. The reaction mixture was warmed to room temperature and stirred for an additional 12h, during which time a precipitate formed. A solution of KOH (1M, 50mL, 50mmol) was added causing the precipitate to disappear and a clear biphasic solution was formed. The organic layer was separated, dried over anhydrous MgSO4, filtered and concentrated at reduced pressure to afford the crude product. The analytically pure imidazolines 7 were obtained by a brief crystallization from EtOAc/hexane. All imidazolines 7 used in subsequent Pd-catalyzed N-arylation are known compounds except for 7a-c.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 84,p. 160 - 172
[2]Journal of Enzyme Inhibition and Medicinal Chemistry,2016,vol. 31,p. 197 - 202

67
[ 34328-46-6 ]
6-methoxy-5-morpholino-2,3-dihydro-1H-inden-1-one [ No CAS ]
(E)-2-(4-chloro-3-(trifluoromethyl)benzylidene)-6-methoxy-5-morpholino-2,3-dihydro-1H-inden-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 120℃; for 6h;	To a solution of 13 (100 mg, 0.404 mmol) in toluene 10 mL was added <strong>[34328-46-6]4-chloro-3-(trifluoromethyl)benzaldehyde</strong> 87 (84.4 mg, 0.404 mmol). PTSA (153.8 mg, 0.808 mmol) was added and the reaction was stirred at 120 C. for 6 h. The reaction mass was diluted with ethyl acetate and washed with water (3×25 mL). The organic layer was dried over sodium sulphate and concentrated to get the crude 88 which was purified through flash chromatography by using 100-200 mesh silica gel. The compound (E)-2-(4-chloro-3-(trifluoromethyl)benzylidene)-6-methoxy-5-morpholino-2,3-dihydro-1H-inden-1-one 88 was eluted at 31% ethyl acetate in hexane to afford yellow coloured solid.

Reference： [1]Patent: US2015/72980,2015,A1 .Location in patent: Paragraph 0189; 0190

68
[ 141-82-2 ]
[ 34328-46-6 ]
C₁₀H₉ClF₃NO₂ [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 1207 - 1212

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P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Ghs Hazard Statements

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere