sales@ambeed.com

Structure Search

List Search MOL Search Structure Search

Hello, Sign in

Home Cart 0 Sign in

X

[ CAS No. 1535-73-5 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 1535-73-5

Chemical Structure| 1535-73-5

Chemical Structure| 1535-73-5

Structure of 1535-73-5 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 1535-73-5 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1535-73-5 ]

SDS Specification

Alternatived Products of [ 1535-73-5 ]

Product Details of [ 1535-73-5 ]

CAS No. :	1535-73-5	MDL No. :	MFCD00041511
Formula :	C₇H₆F₃NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SADHVOSOZBAAGL-UHFFFAOYSA-N
M.W :	177.12	Pubchem ID :	73753
Synonyms :

Calculated chemistry of [ 1535-73-5 ]

Physicochemical Properties

Num. heavy atoms :	12
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 :	37.53
TPSA :	35.25 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) :	-5.86 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.65
Log Po/w (XLOGP3) :	2.14
Log Po/w (WLOGP) :	3.44
Log Po/w (MLOGP) :	1.64
Log Po/w (SILICOS-IT) :	1.67
Consensus Log Po/w :	2.11

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.52
Solubility :	0.53 mg/ml ; 0.00299 mol/l
Class :	Soluble
Log S (Ali) :	-2.51
Solubility :	0.545 mg/ml ; 0.00308 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.66
Solubility :	0.385 mg/ml ; 0.00217 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.47

Safety of [ 1535-73-5 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H312-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1535-73-5 ]

* 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 [ 1535-73-5 ]
Downstream synthetic route of [ 1535-73-5 ]

[ 1535-73-5 ] Synthesis Path-Upstream 1~13

1
[ 914636-35-4 ]
[ 1535-73-5 ]

Reference： [1] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 5, p. 373 - 377

2
[ 39065-91-3 ]
[ 1535-73-5 ]

Reference： [1] European Journal of Organic Chemistry, 2008, # 17, p. 2875 - 2880

3
[ 95-57-8 ]
[ 1535-73-5 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1986, # 6, p. 925 - 929

4
[ 766-51-8 ]
[ 1535-73-5 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1986, # 6, p. 925 - 929

5
[ 97608-46-3 ]
[ 1535-73-5 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1986, # 6, p. 925 - 929

6
[ 450-96-4 ]
[ 1535-73-5 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1986, # 6, p. 925 - 929

7
[ 450-96-4 ]
[ 1535-73-5 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 12, p. 4160 - 4184

8
[ 1535-73-5 ]
[ 2995-45-1 ]

Reference： [1] Journal of Organic Chemistry, 2015, vol. 80, # 16, p. 7876 - 7883

9
[ 1535-73-5 ]
[ 959235-95-1 ]

Reference： [1] Journal of Medicinal Chemistry, 1998, vol. 41, # 10, p. 1598 - 1612

10
[ 1535-73-5 ]
[ 467451-91-8 ]

Reference： [1] Journal of Medicinal Chemistry, 1998, vol. 41, # 10, p. 1598 - 1612
[2] Patent: WO2009/133387, 2009, A1,

11
[ 1535-73-5 ]
[ 198206-33-6 ]

Yield	Reaction Conditions	Operation in experiment
14%	Stage #1: With sulfuric acid; sodium nitrite In water at -5℃; for 0.25 h; Stage #2: With potassium iodide In water at 20℃;	l-Iodo-3-(trifluoromethoxy)benzene:; To 3-(trifluoromethoxy)beπzenamine (17.7 g, 100.00 mmol) was added a solution OfNaNO₂ (7.4 g, 115.62 mmol) in H₂O (80 ml). H₂SO₄ (25 g, 250.00 mmol) was added dropwise with stirring at -5 °C. The resulting solution was kept at -5 °C for 15 minutes. To this solution was added a solution of KI (20 g, 120,48 mmol) in H₂O (60 ml) dropwise, The resulting solution was stirred overnight at room temperature and extracted with EtOAc (2 X 100 mL). The combined organic layers were washed with Na₂SO₃/H₂O (2 X 50 mL), dried over Na₂SO₄ and concentrated in vacuo. The residue was purified by silica gel column chromatography to afford 4.0 g (14percent) of l-iodo-3- (trifluoromethoxy)benzene.

Reference： [1] Patent: WO2006/55187, 2006, A1, . Location in patent: Page/Page column 99-100

12
[ 1535-73-5 ]
[ 887267-47-2 ]

Reference： [1] Patent: WO2009/3077, 2008, A1, . Location in patent: Page/Page column 140

13
[ 1535-73-5 ]
[ 116369-25-6 ]
[ 887267-47-2 ]

Reference： [1] Patent: WO2011/3684, 2011, A1, . Location in patent: Page/Page column 25

[ 1535-73-5 ] Synthesis Path-Downstream 1~39

1
[ 450-96-4 ]
bis-<(trifluoromethoxy)phenyl> amine [ No CAS ]
[ 1535-73-5 ]

Reference： [1]Bulletin de la Societe Chimique de France,1986,p. 925 - 929

2
[ 51673-84-8 ]
[ 1535-73-5 ]
(2,2-Dimethoxy-ethyl)-(3-trifluoromethoxy-phenyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 760.051 Torr; for 16h;	Glyoxyl dimethyl acetal (1.27 g, 12.2 mmol, 2.2 eq) was added to 3- trifluoromethoxyaniline (1.00 g, 5.7 mmol, 1.0 eq) in EtOH (15 ml). Palladium on charcoal (10% w/w; 0.20 g) was added and the reaction was placed under hydrogen (1 atmosphere). The reaction was stirred at room temperature for 16 h. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was taken up in brine (20 ml) and the product was extracted with EtOAc (3 x 20 ml). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to provide (1) as a yellow oil (1.43 g, 4.9 mmol, 86%).

Reference： [1]Patent: WO2010/1179,2010,A2 .Location in patent: Page/Page column 56
[2]Journal of Medicinal Chemistry,1998,vol. 41,p. 1598 - 1612

3
[ 1147550-11-5 ]
[ 1535-73-5 ]
[ 235101-42-5 ]

Yield	Reaction Conditions	Operation in experiment
30%	With hydrogenchloride; sodium hydrogensulfite at 90℃;

Reference： [1]Jimonet, Patrick; Audiau, François; Barreau, Michel; Blanchard, Jean-Charles; Boireau, Alain; Bour, Yvette; Coléno, Marie-Annick; Doble, Adam; Doerflinger, Gilles; Do Huu, Claudine; Donat, Marie-Hélène; Duchesne, Jean Marie; Ganil, Pierre; Guérémy, Claude; Honoré, Eliane; Just, Bernard; Kerphirique, Roselyne; Gontier, Sylvie; Hubert, Philippe; Laduron, Pierre M.; Blevec, Joseph Le; Meunier, Mireille; Miquet, Jean-Marie; Nemecek, Conception; Pasquet, Martine; Piot, Odile; Pratt, Jeremy; Rataud, Jean; Reibaud, Michel; Stutzmann, Jean-Marie; Mignani, Serge [Journal of Medicinal Chemistry, 1999, vol. 42, # 15, p. 2828 - 2843]

4
[ 1535-73-5 ]
[ 126067-60-5 ]
5-methyl-1-(3-trifluoromethyl-phenyl)-1<i>H</i>-pyrazole-3-carboxylic acid (3-trifluoromethoxy-phenyl)-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane

Reference： [1]Kordik, Cheryl P.; Luo, Chi; Zanoni, Brian C.; Lovenberg, Timothy W.; Wilson, Sandy J.; Vaidya, Anil H.; Crooke, Jeffrey J.; Rosenthal, Daniel I.; Reitz, Allen B. [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 17, p. 2287 - 2290]

5
[ 14109-72-9 ]
[ 1535-73-5 ]
2-methyl-4-(trifluoromethoxy)-1H-indole [ No CAS ]
[ 57330-49-1 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: methylsulfanyl-acetone; m-trifluoromethoxyaniline With tert-butylhypochlorite; triethylamine at 0℃; Stage #2: With nickel In ethanol
1: 58.1% 2: 28.7%	Stage #1: m-trifluoromethoxyaniline With tert-butylhypochlorite In dichloromethane at -78℃; for 0.166667h; Stage #2: methylsulfanyl-acetone In dichloromethane at -78℃; for 1h; Further stages;

Reference： [1]Liu, Kun; Black, Regina M.; Acton III, John J.; Mosley, Ralph; Debenham, Sheryl; Abola, Ramon; Yang, Meng; Tschirret-Guth, Richard; Colwell, Lawrence; Liu, Cherrie; Wu, Margaret; Wang, Chuanlin F.; MacNaul, Karen L.; McCann, Margaret E.; Moller, David E.; Berger, Joel P.; Meinke, Peter T.; Jones, A. Brian; Wood, Harold B. [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2437 - 2440]
[2]Location in patent: experimental part Acton III, John J.; Akiyama, Taro E.; Chang, Ching H.; Colwell, Lawrence; Debenham, Sheryl; Doebber, Thomas; Einstein, Monica; Liu, Kun; McCann, Margaret E.; Moller, David E.; Muise, Eric S.; Tan, Yugen; Thompson, John R.; Wong, Kenny K.; Wu, Margaret; Xu, Libo; Meinke, Peter T.; Berger, Joel P.; Wood, Harold B. [Journal of Medicinal Chemistry, 2009, vol. 52, # 13, p. 3846 - 3854]

6
[ 1535-73-5 ]
[ 959235-95-1 ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 1598 - 1612

7
[ 1535-73-5 ]
[ 467451-91-8 ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 1598 - 1612
[2]Patent: WO2009/133387,2009,A1

8
[ 6160-65-2 ]
[ 1535-73-5 ]
[ 471937-78-7 ]

Yield	Reaction Conditions	Operation in experiment
50%	In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 1.5h;	IV [0147] A solution of 3.46 g (19.5 mM) of 3-(trifluoromethoxy)aniline in 150 ml of dimethylformamide is prepared and is cooled to 0° C. A solution of 3.83 g (21.45 mM) of thiocarbonyldiimidazole dissolved in 60 ml of dimethylformamide is then added dropwise. The reaction mixture is agitated at ordinary temperature for 1 hour 30 minutes, then poured onto 300 ml of water, and extracted with twice 100 ml of ethyl ether. These organic phases are washed with twice 50 ml of water, dried over magnesium sulphate and then concentrated under reduced pressure. This residue is purified by chromatography on silica gel in eluting with the aid of a cyclohexane/ethyl acetate mixture (95/5; v/v). 2.1 g of product sought after are thus obtained as a green-yellow liquid (yield=50%). [0148] 1H NMR (CDCl3, 300 MHz): 7.38 (t, 1H); 7.15 (m, 3H)

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - US2004/116417, 2004, A1 Location in patent: Page/Page column 7

9
[ 1535-73-5 ]
[ 116369-25-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With N-Bromosuccinimide In DMF (N,N-dimethyl-formamide) at 20℃;	59.a Example 59; Synthesis of 4-[(1-benzylpiperidin-4-yl)amino]-2-(trifluoromethoxy)benzamide; (a) Synthesis of 4-bromo-3-(trifluoromethoxy)aniline (a) Synthesis of 4-bromo-3-(trifluoromethoxy)aniline A solution of N-bromosuccinimide (3.78 g, 21.2 mmol) in N,N-dimethylformamide (11 ml) was added dropwise to a solution of 3-trifluoromethoxyaniline (3.84 g, 21.2 mmol) in N,N-dimethylformamide (11 ml) at room temperature over a period of 40 minutes. After completion of the dropwise addition, the resulting mixture was stirred overnight. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated and the crude product thus obtained was purified by a silica gel column chromatography (hexane/chloroform = 6/4) to obtain 4-bromo-3-(trifluoromethoxy)aniline (4.96 g, 91%).
68%	With pyridinium hydrobromide perbromide In dichloromethane at 0℃; for 3h; Inert atmosphere;

Reference： [1]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical) - EP1500643, 2005, A1 Location in patent: Page 35
[2]Location in patent: experimental part Park, Cheol-Min; Bruncko, Milan; Adickes, Jessica; Bauch, Joy; Ding, Hong; Kunzer, Aaron; Marsh, Kennan C.; Nimmer, Paul; Shoemaker, Alexander R.; Song, Xiaohong; Tahir, Stephen K.; Tse, Christin; Wang, Xilu; Wendt, Michael D.; Yang, Xiufen; Zhang, Haichao; Fesik, Stephen W.; Rosenberg, Saul H.; Elmore, Steven W. [Journal of Medicinal Chemistry, 2008, vol. 51, # 21, p. 6902 - 6915]

10
[ 463-71-8 ]
[ 1535-73-5 ]
[ 471937-78-7 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 1h;	13.B To a solution of 3-trifluoromethyoxyphenylaniline (0.2 mmol, 35 mg, 27 uL) and DIEA (0.5 mmol, 87 pL) in 0.5 mL of CH2Cl2 was added thiophosgene (0.2 mmol, 15 AL) via syringe. The solution was allowed to stand at ambient temperature for 1 h, and the title compound in Example 13, Step A (0.2 mmol, 65 mg) was added. The reaction mixture was heated at 40 °C for 1 h, then Hg (O2CCF3) 2 was added. The reaction was heated at 40 °C for 2 h, and allowed to stand at ambient temperature for 16 h. The slurry was poured into EtOAc and saturated NaHC03 containing Na2S, then filtered through celite. The organic phase was dried with Na2SO4 and concentrated in vacuo. Flash chromatography on silica eluting with 20% and 35% EtOAc in hexanes afforded the product as a beige solid. LC-MS (ESI, Method B) 2.14 min, m/z 524. 1 (M + 1).
	With sodium hydrogencarbonate In dichloromethane; water at 0 - 20℃;	Preparation of 2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-4-one (24a) General procedure: a) To a stirred mixture of 3-(trifluoromethyl)aniline (22a, 10.5 g, 60 mmol) and NaHCO3 (25.2 g, 300 mmol) in mixed-solvent of dichloromethane (100 mL) and H2O (200 mL) was dropwise added the solution of thiophosgene (9.660 g, 84 mmol) in dichloromethane (100 mL) at 0 °C. Then the mixture was stirred overnight at room temperature (RT). The reaction mixture was stirred overnight at room temperature. After the reaction was complete as monitored by thin layer chromatography (TLC), the reaction mixture was diluted with dichloromethane (300 mL). The resulting solution was washed with H2O (80 mL) and brine (80 mL). The organic layer was separated and dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a yellow oil 23a (8.62 g). The crude product was used in next step without further purification.
	With sodium hydrogencarbonate In dichloromethane; water at 25℃; for 12h;	1.1 Step 1: l-Isothiocyanato-3-(trifluoromethoxy)benzene To a solution of 3-(trifluoromethoxy)aniline (300 mg,1.69 mmol, 225.56 pL,1 eq) and NaHCCL (569.16 mg, 6.77 mmol, 263.50 pL, 4 eq) in DCM (10 mL) and H20 (10 mL) was added thiocarbonyl dichloride (389.50 mg, 3.39 mmol, 259.66 pL, 2 eq) at 0 °C. The mixture was stirred at 25 °C for 12 h. TLC (PE/EtOAc = 10/1, Rf = 0.47) indicated the starting material was consumed completely and one new spot formed. The reaction mixture was quenched by addition of sat. aq. NaHCCh (30 mL), extracted with DCM (30 mL x 3). The combined organic layers were washed with brine (10 mL), dried over Na2S04, filtered and concentrated under reduced pressure below 30 °C to yield l-isothiocyanato-3-(trifluoromethoxy)benzene (371 mg, crude) as yellow oil, which was used in the next step without further purification. ES-LCMS no desired m/z was detected.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2005/65680, 2005, A1 Location in patent: Page/Page column 66-67
[2]Chen, Yun; Deng, Xianming; He, Hongbin; Hu, Zhiyu; Huang, Huiying; Jiang, Hua; Li, Li; Xu, Qingyan; Zhou, Rongbin [Bioorganic and medicinal chemistry letters, 2020, vol. 30, # 7]
[3]Current Patent Assignee: IKENA ONCOLOGY INC - WO2021/127301, 2021, A1 Location in patent: Paragraph 00221; 00305

11
[ 1535-73-5 ]
[ 214470-37-8 ]
4-[(3-Trifluoromethoxyphenyl)amino]-6-nitro-3-quinolinecarbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; ethyl acetate	4-[(3-Trifluoromethoxyphenyl)amino]-6-nitro-3-quinolinecarbonitrile 4-[(3-Trifluoromethoxyphenyl)amino]-6-nitro-3-quinolinecarbonitrile A mixture of 5.00 g (21.5 mmol) 4-chloro-6-nitro-3-quinolinecarbonitrile, 200 ml ethanol, and 3.4 ml (25.3 mmol) 3-trifluoromethoxyaniline was heated to reflux. At 5 hours, removed heat and made basic with saturated sodium bicarbonate. Stripped solvents, slurried residue with hexane, collected, and washed with water. Dissolved in ethyl acetate, stirred with Darco, filtered, stripped solvent, and dried in vacuo, giving 4.537 g of yellow-orange solid: mass spectrum (electrospray m/e): M+H=374.8.
	In ethanol; ethyl acetate	365 4-[(3-Trifluoromethoxyphenyl)amino]-6-nitro-3-quinolinecarbonitrile Example 365 4-[(3-Trifluoromethoxyphenyl)amino]-6-nitro-3-quinolinecarbonitrile A mixture of 5.00 g (21.5 mmol) 4-chloro-6-nitro-3-quinolinecarbonitrile, 200 ml ethanol, and 3.4 ml (25.3 mmol) 3-trifluoromethoxyaniline was heated to reflux. At 5 hours, removed heat and made basic with saturated sodium bicarbonate. Stripped solvents, slurried residue with hexane, collected, and washed with water. Dissolved in ethyl acetate, stirred with Darco, filtered, stripped solvent, and dried in vacuo, giving 4.537 g of yellow-orange solid: mass spectrum (electrospray m/e): M+H = 374.8.

Reference： [1]Current Patent Assignee: PFIZER INC - US6002008, 1999, A Current Patent Assignee: PFIZER INC - US6384051, 2002, B1
[2]Current Patent Assignee: PFIZER INC - EP1263503, 2005, B1

12
[ 1535-73-5 ]
[ 198206-33-6 ]

Yield	Reaction Conditions	Operation in experiment
14%		l-Iodo-3-(trifluoromethoxy)benzene:; To 3-(trifluoromethoxy)be?zenamine (17.7 g, 100.00 mmol) was added a solution OfNaNO2 (7.4 g, 115.62 mmol) in H2O (80 ml). H2SO4 (25 g, 250.00 mmol) was added dropwise with stirring at -5 C. The resulting solution was kept at -5 C for 15 minutes. To this solution was added a solution of KI (20 g, 120,48 mmol) in H2O (60 ml) dropwise, The resulting solution was stirred overnight at room temperature and extracted with EtOAc (2 X 100 mL). The combined organic layers were washed with Na2SO3/H2O (2 X 50 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography to afford 4.0 g (14%) of l-iodo-3- (trifluoromethoxy)benzene.

Reference： [1]Patent: WO2006/55187,2006,A1 .Location in patent: Page/Page column 99-100

13
[ 1535-73-5 ]
[ 887267-47-2 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 12.667h;	A solution of NBS (20.1 g, 111.9 mmol) in DMF (40 mL) was added drop wise to a solution of 3-trifluoromethylaniline (20.0 g, 112.9 mmol) in DMF (80 mL) at room temperature over 40 minutes. The reaction mixture was stirred overnight.After 12 h, the reaction mixture was poured into water and extracted with EtOAc and the organic layer was dried over anhydrous Na2SO4. Concentration in vacuo gave 26 g of Preparation 67A. [00514] MS (ES): m/z = 256.2 [M+lf .

Reference： [1]Patent: WO2009/3077,2008,A1 .Location in patent: Page/Page column 140

14
[ 450-96-4 ]
[ 1535-73-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 4160 - 4184

15
[ 2882-19-1 ]
[ 1535-73-5 ]
[ 1233329-73-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: ethyl 2-phenyl-2-bromoacetate; m-trifluoromethoxyaniline With N-ethyl-N,N-diisopropylamine In acetonitrile at 100℃; for 1h; microwave irradiation; Stage #2: With lithium hydroxide monohydrate; water In acetonitrile at 20℃; for 1h; Stage #3: With hydrogenchloride In 1,4-dioxane; water; acetonitrile	16 Ethyl 2-bromo-2-phenylacetate (400 mg, 1.64 mmol), 3-(trifluoromethoxy)aniline (0.33 mL, 2.47 mmol), and DIPEA (0.43 mL, 2.47 mmol) are dissolved in acetonitrile (5 mL) and heated under MW irradiation at1000C for Ih (Conversion complete by UPLC/MS-UV). Water (5 mL) and lithium hydroxide hydrate (207 mg, 4.94 mmol) are directly added and the resulting mixture is stirred at RT for Ih. Then 4M HCl in dioxane is added to pH 1 , the organic solvents are evaporated and the resulting crude oil is purified by filtration through a silica pad using DCM/MeOH= 9/1 as the eluent. Intermediate 188 is collected as a brown oil (569 mg, quantitative yield).

Reference： [1]Current Patent Assignee: Valline SRL - WO2010/72338, 2010, A1 Location in patent: Page/Page column 78

16
[ 1535-73-5 ]
[ 61940-21-4 ]
[ 1233861-80-7 ]

Yield	Reaction Conditions	Operation in experiment
63%	With acetic acid; In 1,4-dioxane; at 140℃; for 0.333333h;Microwave irradiation;	Example 2. Preparation of Additional N-(3-oxo-2-(optionally substituted phenyl)isoindolin-4-yl) carboxamides of the Invention: Synthesis of 7-nitw-2-(3-(trifluowmethoxy)phenyl)isoindolin-l-one (6):A mixture of <strong>[61940-21-4]methyl 2-(bromomethyl)-6-nitrobenzoate</strong> from Example 1, Step 2 (3; 0.86 g, 3.14 mmol), 3-(trifluoromethoxyl)benzenamine (21; 0.56 g, 3.14 mmol) and HOAc (0.3 mL) in dioxane (3 mL) was stirred in microwave at 140 0C for 20 min. The mixture was adjust to pH=7 and extracted with ethyl acetate (3 x 25 mL). The combined organic layers were dried over Na2SO4, concentrated in vacuo and purified by chromatography on silica gel to afford 7-nitro-2-(3- (trifluoromethoxy)phenyl)isoindolin-l-one 6 (0.67 g, 1.98 mmol, 63%). MS (ESI) calcd for Ci5H9F3N2O4: 338; found: 339 [M+H]. 7-nitro-2-(3- (trifluoromethoxy)phenyl)isoindolin-l-one 6 was converted to the corresponding amine and then coupled to various acids as in Steps 3-4 of Example 1 to producevarious compounds of the formula: . See for example, Compound 108.

Reference： [1]Patent: WO2010/77686,2010,A1 .Location in patent: Page/Page column 128

17
[ 1535-73-5 ]
[ 116369-25-6 ]
[ 887267-47-2 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; In toluene; at 20℃; for 2h;	The title compound was prepared according to procedures similar to those described in Example 1 starting from 2-bromo-5-trifluoromethoxy-aniline, which was obtained as follows:A solution of 3-trifluoromethoxy-aniline (1.77 g) in toluene (20 ml) was treated with Lambda/-bromosuccinimide (1.87 g) at ambient temperature and the reaction mixture was stirred for 2 hours at ambient temperature, quenched by addition of water and the mixture extracted with ethyl acetate (3x 50 ml). The combined organic extracts were washed with aqueous sodium hydrogen carbonate (saturated), dried over sodium sulfate and then concentrated in vacuo. The residue was purified by chromatography on silica gel (eluent: cyclohexane / ethyl acetate 95:5) to afford 4-bromo-3-trifluoromethoxy-aniline (270 mg) and 2-bromo-5- trifluoromethoxy-aniline (1.45 g), which were both characterized by mass and NMR spectra. 4-bromo-3-trifluoromethoxy-aniline: MS (ES+) 256 / 258 (MH+); IH NMR (400 MHz, CDCl3) 3.5 (brs, 2H), 6.5 (d, IH), 6.7 (s, IH), 7.3 (d, IH). 2-bromo-5-trifluoromethoxy- aniline: MS (ES+) 256 / 258 (MH+); IH NMR (400 MHz, CDCl3) 4.2 (brs, 2H), 6.5 (d, IH), 6.6 (s, IH), 7.4 (d, IH).

Reference： [1]Patent: WO2011/3684,2011,A1 .Location in patent: Page/Page column 25

18
[ 95095-84-4 ]
[ 1535-73-5 ]
1-((m-trifluoromethoxy)phenyl)-3-(6-chloro-2-cyan-3-pyridyl)triazene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%		To an ice-salt bathcooled solution of 3 (7.65 g, 50.0 mmol), hydrochloric acid (150 mL), a solution of sodium nitrite (3.6 g, 50.0mmol, 50 mL/H2O) was added dropwise, the mixture was left to stir for 30 minutes, followed by addition of 3-trifluromethoxyalinine dissolved in 50 mL alcohol, and neutralized with sodium acetate, the mixture was stirredfor 2 hours while the reaction temperature was kept between -5 to 0 C, before pouring into 2000 mL cold waterand stirring, the solid was filtered and washed with water until the filtrate was colorless, the crude productobtained was recrystallized with ethyl acetate to give 8.55 g 4 as orange-yellow solid (50%).
		General procedure: A mixture of 2,6-dichloro-3-nitropyridine (7) (26 mmol), cuprous cyanide (0.59mml) and appropriate amount of N-methylpyrrolidone was heated at 180 C for 15 min, then cooled to 10 C and poured into ice-water (200mL) and stirred for 30 min. The solution was then filtered, washed with water and dried. The resulting 2-cyano-3-nitro-6-chloropyridine (8) was extracted with boiling toluene (50mL) for 3 times, combined the organic phases and washed with water and saturated sodium chloride solution. Then the organic phase was dried, filtered, evaporated under reduced pressure to dryness, and purified by recrystallization with a mixture of petroleum ether/ethyl acetate (4/1). The reduction of the intermediate 8 (10mmol) was reacted with sodium hyposulfite (80 mmol, and 40 mmol 2 h later) in dichloromethane/aqua (20mL/20mL) solution, and added TBAB (1mmol) as a phase-transfer catalyst. The mixture was stirred at room temperature for 3 h, and then extracted with dichloromethane (40mL) for 3 times. The combined organic phase was dried with anhydrous magnesium sulfate, filtered and evaporated under reduced pressure to yield 2-cyano-6-chloro-3-pyridinylamine (9). Compound 9 was added into 3mL of hydrochloric acid (10 mol/L), and the aqueous solution of sodium nitrite (0.072g/1.0mL) was added dropwise under stirring for 20 min in an ice-salt bath. The diazonium solution was reacted with the corresponding substituted anilines (10.0mmol) and then neutralized with excess of sodium acetate trihydrate, stirred for 2 h at 0 C. The solution was kept overnight, filtered, and washed with water to yield the crude products. The crude products were then purified by recrystallization with ethyl acetate to obtain intermediates 1-substituted-3-(2-cyano-6-chloro-3-pyridyl)triazene (10a-10j). The intermediates 10a-10j were boiled in 70% ethanol (25.0 mL) for 1h, and then evaporated under reduced pressure to dryness. Acetic acid (10.0mL) was added and the solution was refluxed for 2h, cooled, poured into water (100mL), filtered and dried. The crude products thus obtained were recrystallized from ethanol to give the final compounds 4-substituted-6-chloro-pyrido[3,2-d][1,2,3]triazines (11a-11j).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 1224 - 1228
[2]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 7807 - 7815

19
[ 2548-29-0 ]
[ 1535-73-5 ]
[ 1589488-22-1 ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 20℃; for 16h;	General procedure: To a solution of anilines (1.2 eq.) in acetonitrile (15 mL) was added compound 5 (1.0 eq.) and the mixture stirred atroom temperature for 16 h. The solid formed was filtered and washed with acetonitrile (5 mL). The filtrate was concentrated to afford residue was subjected to column chromatography on silica gel to yield compound 7 (Yield: 47-78%).

Reference： [1]Journal of the Korean Chemical Society,2013,vol. 57,p. 731 - 737

20
[ 3279-90-1 ]
[ 1535-73-5 ]
[ 1611467-19-6 ]

Yield	Reaction Conditions	Operation in experiment
68%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; sodium t-butanolate; XPhos In toluene at 100℃; for 9h; Inert atmosphere;	2 4.1.2 General procedure of N-arylation for preparation of diaryl amine compounds: synthesis of 6-[3-(trifluoromethoxy)phenyl]amino}-3,4-dihydroquinolin-2(1H)-one (11i) Toluene (4.5 mL) was added to a flask containing 6-bromo-3,4-dihydroquinolin-2(1H)-one (300 mg, 1.33 mmol), 3-(trifluoromethoxy)aniline (231 μL, 1.73 mmol), Pd2(dba)3 (15.2 mg, 0.02 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (31.6 mg, 0.07 mmol) and NaOt-Bu (192 mg, 2.00 mmol) under an argon atmosphere. The mixture was stirred at 100 °C for 9 h. After cooling, the reaction mixture was diluted with EtOAc, and filtered through a pad of Celite. The filtrate was concentrated in vacuo. Crude material was purified by flash chromatography with n-hexane/EtOAc (2:3) to afford the desired diaryl amine 11i (292 mg, 68% yield): pale yellow solid; mp 160-162 °C; IR (neat) cm-1: 1667 (C=O), 3219 (NH), 3315 (NH); 1H NMR (500 MHz, DMSO-d6) δ 2.43 (t, J = 6.9 Hz, 2H; CH2), 2.85 (t, J = 6.9 Hz, 2H; CH2), 6.63 (d, J = 8.0 Hz, 1H; Ar), 6.79 (s, 1H; Ar), 6.81 (d, J = 8.0 Hz, 1H; Ar), 6.91-6.96 (m, 3H; Ar), 7.25 (t, J = 8.0 Hz, 1H; Ar), 8.25 (s, 1H; NH), 9.99 (s, 1H; NH); 13C NMR (125 MHz, DMSO-d6) δ 25.0, 30.4, 106.3, 109.6, 113.1, 115.8, 118.7, 119.5, 120.1 (q), 124.7, 130.7, 133.1, 136.1, 146.9, 149.4, 169.8; Anal. Calcd for C16H13F3N2O2: C, 59.63; H, 4.07; N, 8.69. Found: C, 59.51; H, 4.12; N, 8.59.

Reference： [1]Takeuchi, Tomoki; Oishi, Shinya; Kaneda, Masato; Misu, Ryosuke; Ohno, Hiroaki; Sawada, Jun-Ichi; Asai, Akira; Nakamura, Shinya; Nakanishi, Isao; Fujii, Nobutaka [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 12, p. 3171 - 3179]

21
[ 1535-73-5 ]
[ 2995-45-1 ]

Reference： [1]Journal of Organic Chemistry,2015,vol. 80,p. 7876 - 7883

22
[ 3140-73-6 ]
[ 1535-73-5 ]
[ 1874274-26-6 ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium carbonate In tetrahydrofuran at 70℃; for 4h;	General procedure for the synthesis of substituted 4,6-dimethoxy-N-phenyl-1,3,5-triazin-2-amines (4a-x) General procedure: 2-Chloro-4,6-dimethoxy-1,3,5-triazine (1 mmol) (2), substituted aniline (1 mmol)/heterocyclic amines (3) (1 mmol), anhydrous K2CO3 (2 mmol) were added in dry THF (5 mL) taken in a round bottom flask. The reaction mixture was refluxed at 70 °C for 4 h. After completion of the reaction the product is confirmed on thin-layer chromatography (TLC) using eluent (2:8 mL,ethyl acetate-hexane). The reaction mixture was quenched with water and the crude product was extracted with ethyl acetate (3 times) and organic layer was separated and dried over anhydrous Na2SO4. The solvent evaporated on rotavapour. The Crude material was purified by column chromatography (ethylacetate-n-hexane) and product 4(a-x) with good yield (70-75 %) were obtained (Scheme-II).

Reference： [1]Shinde, Ravindra S.; Salunke, Shridhar D. [Asian Journal of Chemistry, 2015, vol. 27, # 11, p. 4130 - 4134]

23
[ 128577-47-9 ]
[ 1535-73-5 ]
methyl 3-fluoro-4-(((3-(trifluoromethoxy)phenyl)amino)methyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65.8%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 16h;	[2598] A solution of 3-(trifluoromethoxy)aniline (0.500 g, 2.823 mmol) and N.N-diisopropylethylamine (0.739 mL, 4.234 mmol) in acetonitrile ( 10 mL) was mixed at the room temperature with methyl 4-(bromomethyl)-3-fliiorobenzoate (0.704 g, 2.851 mmol). The reaction mixture was stirred at the same temperature for 16 hr, concentrated under the reduced pressure to remove the solvent, and water was added to the concentrate, followed by extraction with dichloromethane. The bi-phasic mixture was passed through a plastic frit to remove solid residues and aqueous layer, and the organic layer collected was concentrated in vacuo. The concentrate was purified and concentrated by column chromatography (Si02, 24 g cartridge; ethyl acetate / hexane = 0 % to 10 %) to give the title compound methyl 3- fluoro-4-(((3-(trifluoromethoxy)phenyl)amino)methyl)benzoate as white solid (0.638 g, 65.8 %).

Reference： [1]Patent: WO2017/23133,2017,A2 .Location in patent: Paragraph 2596-2598

24
[ 84348-38-9 ]
[ 1535-73-5 ]
(S)-2-(3-trifluoromethoxy-phenylcarbamoyl)-4-methylene-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5717 - 5735

25
[ 1535-73-5 ]
[ 203866-15-3 ]
C₁₇H₁₉F₅N₂O₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5717 - 5735

26
[ 1535-73-5 ]
[ 174148-03-9 ]
C₃₂H₃₂F₃N₃O₆ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5717 - 5735

27
[ 1158098-73-7 ]
[ 1535-73-5 ]
2-methyl-propane-2-sulfinic acid [3-(3-trifluoromethoxy-phenylamino)-oxetan-3-yl]-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	In methanol; at 60℃; for 6h;Inert atmosphere;	General procedure: To a stirred solution of substituted aniline (1 eq) in methanol (3 mL), <strong>[1158098-73-7]oxetan-3-tert-butylsulfinimine</strong> (1.5 eq) was added under argon atmosphere. Reaction mixture was heated at 60 C for appropriate time (Table 2). After the completion of reaction (TLC), reaction mixture was then concentrated. To the resulting residue water was added and then extracted with ethyl acetate (2 X 3 mL). Organic layer was then dried over anhydrous sodium sulphate and filtered. Solvent was removed under reduced pressure. The resulting products were then purified by chromatography using n-hexane-ethyl acetate (7:3) to afford pure 2-methyl-N-[(3-phenylamino)oxetan-3-yl]-2-propanesulfinamide derivatives. All synthesized compounds were characterized by IR, 1H-NMR, HRMS and 13C-NMR spectroscopic techniques.

Reference： [1]Chemical Papers,2017,vol. 71,p. 2435 - 2443

28
[ 89250-26-0 ]
[ 1535-73-5 ]
C₁₇H₁₂F₃N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20℃; for 12h;	3-Phenoxy-N-((5-phenyloxazol-2-yl)methyl)aniline (16a) General procedure: A mixture of 3-phenoxyaniline (0.20 g, 18.0 mmol)and 13a (0.20 g, 18.0 mmol) was dissolved in DMF (10 mL), followed by the addition of potassiumcarbonate (0.90 g, 6.48 mmol) and KI. The solution was stirred at room temperature for 12 h andthen poured into water and extracted with ethyl acetate. The combined organic layers were washedwith water and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified bychromatography on silica gel (petroleum ether:ethyl acetate = 4:1) to give 16a (0.26 g, 70.3%) as acolourless oil.

Reference： [1]Wang, Xinran; Lin, Xuehua; Xu, Xuanqi; Li, Wei; Hao, Lijuan; Liu, Chunchi; Zhao, Dongmei; Cheng, Maosheng [Molecules, 2017, vol. 22, # 11]

29
[ 4010-81-5 ]
[ 1535-73-5 ]
6-morpholino-N-(3-(trifluoromethoxy)phenyl)-9H-purin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.6%	With trifluoroacetic acid; In 2,2,2-trifluoroethanol; at 140℃; for 1.5h;Microwave irradiation;	General procedure: To a stirred suspension of 50 mg 2-cholro analogues 1, 4, 6 or9 (1 equiv) and aromatic amine (2 equiv) in 2mL of 2,2,2-trifluoroethanol (TFE) was added TFA (40 ml) dropwise. The reagents were placed in a sealed microwave vial and the reactions were performed under microwave irradiation (140 C for 90 min). The solventwas removed in vacuo and the residue was re-dissolved in dichloromethane (CH2Cl2) (10 mL). The solution was washed with saturated sodium bicarbonate solution (3 x 10 mL), and the aqueous extracts were combined and washed with CH2Cl2 (10 mL). The combined organic layers were dried with sodium sulfate anhydrous (Na2SO4). The solvent was removed under reduced pressure and the crude material was purified by column chromatographyon silica gel.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 151,p. 836 - 848

30
[ 762260-63-9 ]
[ 1535-73-5 ]
7-bromo-2-oxo-N-(3-(trifluoromethoxy)phenyl)-1,2-dihydroquinoline-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	Stage #1: 7-bromo-2-oxo-1,2-dihydroquinoline-4-carboxylic acid With 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate; triethylamine In dichloromethane at 20℃; for 0.5h; Stage #2: m-trifluoromethoxyaniline In dichloromethane at 20℃;	5.1.3. General synthetic method for compounds (3a-d) General procedure: The carboxylic acid (0.8 mmol), HATU (hexafluorophosphateazabenzotriazole tetramethyl uranium) (455 mg, 1.2 mmol) and triethylamine (324 mg, 3.2 mmol) were stirred for 30 min in 20 mL dichloromethane. The corresponding amine (1.19 mmol) was added to the reaction mixture and stirred overnight. The resulting solid was filtered, washed with dichloromethane and crystallized from methanol unless otherwise noted. Purification was carried out over silica gel chromatography till purity reached >95%.

Reference： [1]Shahin, Mai I.; Roy, Joyeeta; Hanafi, Maha; Wang, Dongyao; Luesakul, Urarika; Chai, Yifeng; Muangsin, Nongnuj; Lasheen, Deena S.; Abou El Ella, Dalal A.; Abouzid, Khaled A.; Neamati, Nouri [European Journal of Medicinal Chemistry, 2018, vol. 155, p. 516 - 530]

31
[ 1214264-88-6 ]
[ 1535-73-5 ]
2-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazaborinine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21.3 mg	With tert.-butylnitrite; sodium acetate; tetra-(n-butyl)ammonium iodide; dibenzoyl peroxide; In acetonitrile; at 80℃;Schlenk technique; Inert atmosphere;	General procedure: In air, Bpin-B(dan) (0.1 mmol, 1.0 eq.), aryl amide (0.2 mmol, 2.0 eq.), TBAI (0.01 eq.),NaOAc (0.15 eq.), and BPO (0.01 eq.) were sequentially weighed and added to a screw-cappedSchenk tube containing a magnetic stir bar. The vessel was evacuated and refilled with nitrogen forthree times. t-BuONO (0.2 eq.) and MeCN (0.6 mL) were added in turn under N2 atmosphere usingsyringes through a septum which was temporarily used to replace the screw cap. The reaction mixturewas then vigorously stirred at 80 C for the indicated time. The resulting mixture was filtered through a pad of Celite, and the filter cake was washed with ethyl acetate (3 mL x 2). The combined filtratewas evaporated under vacuum to dryness and the residue was purified by column chromatography toyield the desired product.

Reference： [1]Molecules,2019,vol. 24

32
[ 3886-08-6 ]
[ 1535-73-5 ]
tert-butyl (S)-4-(((benzyloxy)carbonyl)amino)-5-oxo-5-((3-(trifluoromethoxy)phenyl)amino)pentanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃;

Reference： [1]Wang, Zhen; Zhang, Min; Wang, Jin; Ji, Haitao [Journal of Medicinal Chemistry, 2019, vol. 62, # 7, p. 3617 - 3635]

33
[ 1003845-06-4 ]
[ 1535-73-5 ]
[2-[3-(trifluoromethoxy)anilino]pyrimidin-5-yl]boronic acid hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In ethanol; water; at 80℃; for 0.5h;	A 100 mL RBF is charged with <strong>[1003845-06-4](2-chloropyrimidin-5-yl)boronic acid</strong> (5.0 g, 32 mmol), 3-(trifluoromethoxy)aniline (6.7 g, 38 mmol), ethanol (16 mL) and hydrochloric acid (12 M in water, 0.13 mL, 1.6 mmol). The mixture is heated to 80 C for 30 minutes. The flask is removed from heat and water is slowly added to the stirred solution. The heterogeneous solution becomes homogenous and then a spongy precipitate is formed. The solution is diluted with 300 mL EtOH and 800 mL water. The precipitate is isolated by filtration and dried under reduced pressure to obtain the title compound as an off-white solid. ES/MS m/z 300.0 [M+H].

Reference： [1]Patent: WO2019/89512,2019,A1 .Location in patent: Page/Page column 48-49

34
[ 4928-87-4 ]
[ 1535-73-5 ]
N-(3-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 24h;Inert atmosphere;	To a reaction of 1/7-1, 2, 4-triazole-3 -carboxylic acid (226 mg, 2.0 mmol) and 3- (trifluoromethoxy)aniline (0.28 mL, 2.1 mmol) in dry DMF (10 mL) was added 1- hydroxybenzotriazole monohydrate (337 mg, 2.2 mmol) and EDC (N-(3- Dimethylaminopropyl)-N'-ethylcarbodiimide) (422 mg, 2.2 mmol) followed by N- methylmorpholine (0.88 mL, 8.0 mmol via syringe). The mixture was stirred at room temperature under nitrogen and the solids were gradually dissolved. The contents were stirred at room temperature for 24.0 h, and then slowly diluted into iced water and extracted with DCM (2 x 50 mL). The DCM phase was washed with ice cold water (2 x 100 mL). The DCM phase was dried over anhydrous Na2S04, concentrated under reduced pressure and chromatographed on silica gel using EtOAc and Hexanes (50:50) as eluents to get the desired amide 5 (123.8 mg, 23 % yield) as a white solid. -NMK (400 MHz, DMSO-de): <514.89-14.74 (m, 1H), 10.82 (br s, 1H), 8.67 (br s, 1H), 8.00 (br s, 1H), 7.88 (d, J= 8 Hz, 1H), 7.49 (t, J= 8.2 Hz, 1H), 7.11 (d, J= 8 Hz, 1H); 19F-NMR (376 MHz, DMSO-de): <5 -56.69 ppm. MH+ = 273.2 m/z.

Reference： [1]Patent: WO2020/41556,2020,A1 .Location in patent: Page/Page column 30; 35

35
[ 1119-46-6 ]
[ 1535-73-5 ]
C₁₁H₁₂F₃NO [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2020,vol. 59,p. 7921 - 7927
Angew. Chem.,2020,vol. 132,p. 7995 - 8001,7

36
[ 153493-48-2 ]
[ 1535-73-5 ]
6-((3-(trifluoromethoxy)phenyl)amino)[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: 5,6-dichlorofurazano<3,4-b>pyrazine; m-trifluoromethoxyaniline With triethylamine In tetrahydrofuran at 20℃; Stage #2: With potassium hydroxide In tetrahydrofuran; water at 20℃;

Reference： [1]Salamoun, Joseph M.; Garcia, Christopher J.; Hargett, Stefan R.; Murray, Jacob H.; Chen, Sing-Young; Beretta, Martina; Alexopoulos, Stephanie J.; Shah, Divya P.; Olzomer, Ellen M.; Tucker, Simon P.; Hoehn, Kyle L.; Santos, Webster L. [Journal of Medicinal Chemistry, 2020, vol. 63, # 11, p. 6203 - 6224]

37
[ 5241-66-7 ]
[ 1535-73-5 ]
tert-butyl N-[(1R)-3-methylsulfanyl-1-[[3-(trifluoromethoxy)phenyl]carbamoyl]propyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 3h;

Reference： [1]Yamada, Yousuke; Takashima, Hajime; Walmsley, David Lee; Ushiyama, Fumihito; Matsuda, Yohei; Kanazawa, Harumi; Yamaguchi-Sasaki, Toru; Tanaka-Yamamoto, Nozomi; Yamagishi, Junya; Kurimoto-Tsuruta, Risa; Ogata, Yuya; Ohtake, Norikazu; Angove, Hayley; Baker, Lisa; Harris, Richard; Macias, Alba; Robertson, Alan; Surgenor, Allan; Watanabe, Hayato; Nakano, Koichiro; Mima, Masashi; Iwamoto, Kunihiko; Okada, Atsushi; Takata, Iichiro; Hitaka, Kosuke; Tanaka, Akihiro; Fujita, Kiyoko; Sugiyama, Hiroyuki; Hubbard, Roderick E. [Journal of Medicinal Chemistry, 2020, vol. 63, # 23, p. 14805 - 14820]

38
[ 1535-73-5 ]
[ 235101-42-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water; dichloromethane / 12 h / 25 °C 2: ammonium hydroxide / dichloromethane; acetonitrile / 1 h / 30 °C

Reference： [1]Current Patent Assignee: IKENA ONCOLOGY INC - WO2021/127301, 2021, A1

39
[ 1535-73-5 ]
[ 40516-31-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: ethanol / 4 h / 70 °C 2: diphenylether / 0.8 h / 260 °C 3: lithium hydroxide monohydrate; sodium hydroxide / 6 h / 100 °C 4: diphenylether / 0.8 h / 260 °C 5: trichlorophosphate / 1 h / 120 °C

Reference： [1]Zhang, Chao; Tang, Yun-Sang; Meng, Chu-Ren; Xu, Jing; Zhang, De-Liang; Wang, Jian; Huang, Er-Fang; Shaw, Pang-Chui; Hu, Chun [International Journal of Molecular Sciences, 2022, vol. 23, # 11]

Same Skeleton Products

Related Products

Historical Records

Related Functional Groups of
[ 1535-73-5 ]

Fluorinated Building Blocks

[ 461-82-5 ]

4-(Trifluoromethoxy)aniline

Similarity: 0.98

[ 658-89-9 ]

4-(Trifluoromethoxy)benzene-1,2-diamine

Similarity: 0.94

[ 22236-08-4 ]

3-(Difluoromethoxy)aniline

Similarity: 0.93

[ 22236-10-8 ]

4-(Difluoromethoxy)aniline

Similarity: 0.93

[ 1535-75-7 ]

2-(Trifluoromethoxy)aniline

Similarity: 0.90

Aryls

[ 461-82-5 ]

4-(Trifluoromethoxy)aniline

Similarity: 0.98

[ 658-89-9 ]

4-(Trifluoromethoxy)benzene-1,2-diamine

Similarity: 0.94

[ 22236-08-4 ]

3-(Difluoromethoxy)aniline

Similarity: 0.93

[ 22236-10-8 ]

4-(Difluoromethoxy)aniline

Similarity: 0.93

[ 1535-75-7 ]

2-(Trifluoromethoxy)aniline

Similarity: 0.90

Ethers

[ 461-82-5 ]

4-(Trifluoromethoxy)aniline

Similarity: 0.98

[ 658-89-9 ]

4-(Trifluoromethoxy)benzene-1,2-diamine

Similarity: 0.94

[ 22236-08-4 ]

3-(Difluoromethoxy)aniline

Similarity: 0.93

[ 22236-10-8 ]

4-(Difluoromethoxy)aniline

Similarity: 0.93

[ 1535-75-7 ]

2-(Trifluoromethoxy)aniline

Similarity: 0.90

Amines

[ 461-82-5 ]

4-(Trifluoromethoxy)aniline

Similarity: 0.98

[ 658-89-9 ]

4-(Trifluoromethoxy)benzene-1,2-diamine

Similarity: 0.94

[ 22236-08-4 ]

3-(Difluoromethoxy)aniline

Similarity: 0.93

[ 22236-10-8 ]

4-(Difluoromethoxy)aniline

Similarity: 0.93

[ 1535-75-7 ]

2-(Trifluoromethoxy)aniline

Similarity: 0.90

Trifluoromethyls

[ 461-82-5 ]

4-(Trifluoromethoxy)aniline

Similarity: 0.98

[ 658-89-9 ]

4-(Trifluoromethoxy)benzene-1,2-diamine

Similarity: 0.94

[ 1535-75-7 ]

2-(Trifluoromethoxy)aniline

Similarity: 0.90

[ 133115-55-6 ]

(3-(Trifluoromethoxy)phenyl)hydrazine hydrochloride

Similarity: 0.87

[ 133115-72-7 ]

(4-(Trifluoromethoxy)phenyl)hydrazine hydrochloride

Similarity: 0.85

Ghs Precautionary Statements

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
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