[ CAS No. 367-67-9 ] {[proInfo.proName]}

Name: 367-67-9|2-Bromo-5-nitrobenzotrifluoride|98%
Brand: Ambeed
SKU: A119032
Price: 7.0 USD
Availability: InStock
Rating: 97 (30 reviews)

,{[proInfo.pro_purity]}

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

2D 3D

Structure of 367-67-9 * 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 [ 367-67-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 367-67-9 ]

SDS Specification

Alternatived Products of [ 367-67-9 ]

Product Details of [ 367-67-9 ]

CAS No. :	367-67-9	MDL No. :	MFCD00014707
Formula :	C₇H₃BrF₃NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SXEQQBBOAMHOID-UHFFFAOYSA-N
M.W :	270.00	Pubchem ID :	136198
Synonyms :

Calculated chemistry of [ 367-67-9 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	2
Num. H-bond acceptors :	5.0
Num. H-bond donors :	0.0
Molar Refractivity :	47.97
TPSA :	45.82 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.63 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.73
Log Po/w (XLOGP3) :	3.26
Log Po/w (WLOGP) :	4.53
Log Po/w (MLOGP) :	2.68
Log Po/w (SILICOS-IT) :	1.43
Consensus Log Po/w :	2.73

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.75
Solubility :	0.0477 mg/ml ; 0.000177 mol/l
Class :	Soluble
Log S (Ali) :	-3.9
Solubility :	0.0343 mg/ml ; 0.000127 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.52
Solubility :	0.0821 mg/ml ; 0.000304 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	1.89

Safety of [ 367-67-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302+H312+H332-H315-H319	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 367-67-9 ]

* 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 [ 367-67-9 ]
Downstream synthetic route of [ 367-67-9 ]

[ 367-67-9 ] Synthesis Path-Upstream 1~10

1
[ 367-67-9 ]
[ 393-36-2 ]

Yield	Reaction Conditions	Operation in experiment
98.8%	With piperazine; hydrogen In methanol at 80 - 90℃;	To 1 L high pressure hydrogenation reactor followed by adding 300 mL of methanol, 284 g step nitro product, Raney Ni 20 g, piperazine 1.0 g. The hydrogen in the kettle was replaced with hydrogen for 3-4 times, then at a pressure of 0.8-1.0 MPa, 80-90°C until the reaction is no longer hydrogen. The reaction solution is cooled to remove the catalyst, remove the methanol, remove the moisture, Simple distillation of light yellow liquid amino 4-bromo-3-trifluoromethyl aniline 250 g, GC content: 95percent yield of 98.8percent. Raney Ni and solvent methanol can be recycled.

Reference： [1] Patent: CN106905104, 2017, A, . Location in patent: Paragraph 0020; 0022
[2] Journal of the American Chemical Society, 1951, vol. 73, p. 3932

2
[ 367-67-9 ]
[ 1548-61-4 ]

Reference： [1] Angewandte Chemie - International Edition, 2009, vol. 48, # 46, p. 8729 - 8732
[2] Journal of Medicinal Chemistry, 2017, vol. 60, # 7, p. 3082 - 3093

3
[ 392-83-6 ]
[ 367-67-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	at 50 - 60℃;	At room temperature and stirring to 260 g concentrated sulfuric acid (98percent) slowly add 120 g fuming nitric acid, dubbed nitric acid. 50-60°C to the mixed acid slowly add the product of the next step o-bromotrifluorotoluene 390 g, after adding insulation stir, GC detection has no raw materials that For the end of the reaction. Liquid, the upper organic phase washed by alkali to neutral, washed immediately after the bright yellow liquid liquid 2-bromo-5-nitro-trifluorotoluene 450.4 g, GC content: 95percent, yield: 92percent.

Reference： [1] Patent: CN106905104, 2017, A, . Location in patent: Paragraph 0020-0021
[2] Journal of the American Chemical Society, 1951, vol. 73, p. 3932

4
[ 88-17-5 ]
[ 367-67-9 ]

Reference： [1] Patent: CN106905104, 2017, A,

5
[ 777-37-7 ]
[ 367-67-9 ]

Reference： [1] Journal of Organic Chemistry, 1961, vol. 26, p. 2707 - 2710

6
[ 88-16-4 ]
[ 367-67-9 ]

Reference： [1] Journal of Organic Chemistry, 1961, vol. 26, p. 2707 - 2710

7
[ 121-01-7 ]
[ 367-67-9 ]

Reference： [1] Journal of Organic Chemistry, 1961, vol. 26, p. 2707 - 2710

8
[ 367-67-9 ]
[ 89976-12-5 ]

Reference： [1] Journal of Organic Chemistry, 2003, vol. 68, # 14, p. 5534 - 5539

9
[ 823-96-1 ]
[ 367-67-9 ]
[ 89976-12-5 ]

Reference： [1] Tetrahedron Letters, 2000, vol. 41, # 32, p. 6237 - 6240

10
[ 367-67-9 ]
[ 364-11-4 ]

Reference： [1] Journal of the American Chemical Society, 1951, vol. 73, p. 3932

[ 367-67-9 ] Synthesis Path-Downstream 1~88

1
[ 392-83-6 ]
[ 367-67-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sulfuric acid; nitric acid; at 50 - 60℃;	At room temperature and stirring to 260 g concentrated sulfuric acid (98%) slowly add 120 g fuming nitric acid, dubbed nitric acid. 50-60C to the mixed acid slowly add the product of the next step o-bromotrifluorotoluene 390 g, after adding insulation stir, GC detection has no raw materials that For the end of the reaction. Liquid, the upper organic phase washed by alkali to neutral, washed immediately after the bright yellow liquid liquid 2-bromo-5-nitro-trifluorotoluene 450.4 g, GC content: 95%, yield: 92%.

Reference： [1]Patent: CN106905104,2017,A .Location in patent: Paragraph 0020-0021
[2]Journal of the American Chemical Society,1951,vol. 73,p. 3932

2
[ 367-67-9 ]
[ 393-36-2 ]

Yield	Reaction Conditions	Operation in experiment
98.8%	With piperazine; hydrogen; In methanol; at 80 - 90℃; under 6000.6 - 7500.75 Torr;	To 1 L high pressure hydrogenation reactor followed by adding 300 mL of methanol, 284 g step nitro product, Raney Ni 20 g, piperazine 1.0 g. The hydrogen in the kettle was replaced with hydrogen for 3-4 times, then at a pressure of 0.8-1.0 MPa, 80-90C until the reaction is no longer hydrogen. The reaction solution is cooled to remove the catalyst, remove the methanol, remove the moisture, Simple distillation of light yellow liquid amino 4-bromo-3-trifluoromethyl aniline 250 g, GC content: 95% yield of 98.8%. Raney Ni and solvent methanol can be recycled.

Reference： [1]Patent: CN106905104,2017,A .Location in patent: Paragraph 0020; 0022
[2]Journal of the American Chemical Society,1951,vol. 73,p. 3932

3
[ 121-01-7 ]
[ 367-67-9 ]

Reference： [1]Journal of Organic Chemistry,1961,vol. 26,p. 2707 - 2710

4
[ 34420-17-2 ]
[ 367-67-9 ]
1-(2-trifluoromethyl-4-nitrophenyl)-2-phenylethane [ No CAS ]

Reference： [1]Tetrahedron,2002,vol. 58,p. 1465 - 1470

5
[ 367-67-9 ]
[ 544-92-3 ]
[ 320-47-8 ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 6306 - 6310

6
[ 367-67-9 ]
[ 915779-75-8 ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 6306 - 6310

7
[ 367-67-9 ]
4-dodecyloxy-2-trifluoromethylbenzamide [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 6306 - 6310

8
[ 367-67-9 ]
[ 380621-48-7 ]

Reference： [1]Journal of the American Chemical Society,2001,vol. 123,p. 11071 - 11072

9
[ 367-67-9 ]
[ 380621-49-8 ]

Reference： [1]Journal of the American Chemical Society,2001,vol. 123,p. 11071 - 11072

10
[ 367-67-9 ]
4-phenoxy-2-trifluoromethyl-biphenyl [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2001,vol. 123,p. 11071 - 11072

11
[ 367-67-9 ]
4-(4-nitro-phenoxy)-2-trifluoromethyl-biphenyl [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2001,vol. 123,p. 11071 - 11072

12
[ 367-67-9 ]
4-(4-<i>tert</i>-butyl-phenoxy)-2-trifluoromethyl-biphenyl [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2001,vol. 123,p. 11071 - 11072

13
[ 367-67-9 ]
[ 364-11-4 ]

Reference： [1]Journal of the American Chemical Society,1951,vol. 73,p. 3932

14
[ 777-37-7 ]
[ 367-67-9 ]

Reference： [1]Journal of Organic Chemistry,1961,vol. 26,p. 2707 - 2710

15
[ 88-16-4 ]
[ 367-67-9 ]

Reference： [1]Journal of Organic Chemistry,1961,vol. 26,p. 2707 - 2710

16
[ 143651-26-7 ]
[ 367-67-9 ]
4'-(trans-4-pentylcyclohexyl)-2-trifluoromethyl-4-nitrobiphenyl [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91.3%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; benzene; for 12h;Heating / reflux;	First, 100 ml of ethanol containing 6.57 g of <strong>[143651-26-7]4-(trans-4-pentylcyclohexyl)phenylboronic acid</strong> dissolved therein, 100 ml of benzene containing 10.0 g of 2-trifluoromethyl-4-nitrobromobenzene dissolved therein, 37 ml of a sodium carbonate aqueous solution with a concentration of 2 mol/l, and 1.07 g of tetrakis(triphenylphosphine)palladium(0) were put in an argon-replaced 300 ml flask, and stirred under reflux for 12 hours. After the reaction, water and ether were added to the reaction solution for extraction. The resultant ether layer was washed with a saturated brine and dried with sodium sulfate. The solvent was then distilled off. The residue was purified by silica gel column chromatography (eluent:hexane/toluene=4/1), to obtain 14.2 g (Y: 91.3%) of 4'-(trans-4-pentylcyclohexyl)-2-trifluoromethyl-4-nitrobiphenyl. The purity of the resultant compound was 100.0% as measured by GC.

Reference： [1]Patent: US6388146,2002,B1 .Location in patent: Page column 37-38

17
[ 367-67-9 ]
[ 142-25-6 ]
[ 913173-50-9 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; at 80℃; for 18h;Heating / reflux;	A mixture of 2-bromo-5-nitrobenzotrifuoride (Lancaster Synthesis, GmbH; 5.4 g, 20 MMOL) and N, N, N-trimethylethylenediamine (Fluka, Buchs, Switzerland; 2.25 g, 22 MMOL) and N, N- diisopropylethylamine (13.9 mL) is heated at 80C for 18 hours in a steel pressure vessel. The mixture is then cooled, treated with a saturated aqueous solution of sodium hydrogen carbonate (50 mL) and extracted with ethyl acetate (2 x 100 mL). The combined extracts are dried (NA2SO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is used directly without further purification.

Reference： [1]Patent: WO2004/52884,2004,A1 .Location in patent: Page 58

18
[ 367-67-9 ]
[ 75-04-7 ]
[ 1183678-32-1 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 80℃; for 18h;	A mixture of 2-bromo-5-nitrobenzotrifuoride (Lancaster Synthesis, GmbH; 5.4 g, 20 [MMOL)] and a solution of ethylamin in ethanol (50 mL of 2M, 100 [MMOL)] is heated at [80C] for 18 hours in a steel pressure vessel. The mixture is then cooled and the solvent is evaopated off under reduced pressure to yield the crude product which is purified by column chromatography (silica gel, eluent 20% ethyl acetate in hexane) to afford N-ethyl-4-nitro-6- (trifluoromethyl)- benzenamine as yellow oil. This product is dissolved in ethanol (180 mL) and hydrogenated at atmospheric pressure over Raney nickel (0.5 g) at [45C.] The calculated amount of hydrogen is taken up in 50 hours. The mixture is then filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by chromatography (silica gel ; eluent 50% ethyl acetate in hexane) and recrystallised from ether-hexane to give the title compound as a beige crystalline solid. 1 H-NMR (400 MHz, [DMSO-D6)] : [1. 11] (t, 3H), 3.05 (m, 2H), 4.18 (br t, 1 H), 4.66 (br. s, 2H), 6.58-6. 64 (m, 1 H) and 6.68-6. 75 (m, 2H).

Reference： [1]Patent: WO2004/5281,2004,A1 .Location in patent: Page 53

19
[ 367-67-9 ]
[ 59020-10-9 ]
[ 1214376-56-3 ]

Yield	Reaction Conditions	Operation in experiment
		A stirred solution of 2-bromo-5-nitrobenzotrifuoride (Lancaster Synthesis, GmbH; 3.37 g, 12.5 [MMOL)] and [3- (TRI-N-BUTYLSTANNYL)] pyridine (Maybridge Chemical Co. Ltd. , England; 5.0 g, 13.6 [MMOL)] in xylene (75 mL) was purged with argon for 10 minutes at [20C.] Tetrakis (triphenylphosphine) palladium (0) (1.4 g, 1.25 [MMOL)] is then added and the resulting mixture is heated at [130C] for 24 hours under an argon atmosphere. The mixture is then cooled, treated with an aqueous solution of sodium hydroxide (150 mL of 0.1 M) and purged with air for 2 hours. The resulting mixture is then diluted with ethylacetate (200 mL) and filtered. The orgainic phase is then sequentially washed with water (2 x 80 mL) and saturated aqueous sodium chloride (1 x 80 mL), dried [(MGS04),] filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by column chromatography (silica gel, eluent 50% ethyl acetate in hexane) to afford [3- [ (4-NITRO-3- (TRIFLUOROMETHYL) PHENYL]] pyridine. This product is dissolved in ethanol (200 mL) and hydrogenated at atmospheric pressure over Raney nickel (0.23 g) at [22C.] The calculated amount of hydrogen is taken up in 24 hours. The mixture is then filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by chromatography (silica gel ; eluent 50% ethyl acetate in hexane) and recrystallised from ether-hexane to give the title compound as a colourless crystalline solid, m. p. [92-93C.]

Reference： [1]Patent: WO2004/5281,2004,A1 .Location in patent: Page 56

20
[ 930-62-1 ]
[ 367-67-9 ]
C₁₂H₁₀F₃N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 120℃; for 36h;	A mixture of 2-bromo-5-nitrobenzotrifuoride (Lancaster Synthesis, GmbH; 6.0 g, 22 [MMOL)] and 2, 4-dimethylimidazole (10.6, 110 [MMOL)] is heated at [120C] for 36 hours under an argon atmosphere. The mixture is then cooled and the residue is treated with water (150 mL) and extracted with ethyl acetate (3 x 80 mL). The combined extracts are washed (brine), dried (MgSO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by column chromatography (silica gel, eluent ethyl acetate) to afford 1- [[4-NITRO-2- (TRIFLUOROMETHYL) PHENYL]-1 H-IMIDAZOLE] as yellow crystalline solid. This product is dissolved in ethanol (290 mL) and hydrogenated at atmospheric pressure over Raney nickel (1. 15 g) at [25C.] The calculated amount of hydrogen is taken up in 14 hours. The mixture is then filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by recrystallisation from ether-hexane to give the title compound as a crystalline solid, m. p. [163-164C.]

Reference： [1]Patent: WO2004/5281,2004,A1 .Location in patent: Page 57

21
[ 675-20-7 ]
[ 367-67-9 ]
[ 444002-83-9 ]

Reference： [1]Patent: WO2004/87646,2004,A2 .Location in patent: Page/Page column 111

22
[ 7223-38-3 ]
[ 367-67-9 ]
[ 913173-75-8 ]

Yield	Reaction Conditions	Operation in experiment
	With diisopropylamine;copper(l) iodide; bis(benzonitrile)palladium(II) dichloride; tri-tert-butyl phosphine; In 1,4-dioxane; at 20℃; for 72h;	Step 26.2: Dimethyl-f3-(4-nitro-2-trifluoromethyl-phenyl)-prop-2-vnyll-amine; J-Bu3P (0.25 M in dioxane, 8.9 mL, 2.2 mmol, 0.2 equiv), 3-dimethylamino-1-propyne (FLUKA) (1.65 mL, 15.6 mmol, 1.4 equiv), and /-Pr2NH (2.0 mL, 14.4 mmol, 1.3 equiv) are added sequentially to a mixture of 5-nitro-2-bromobenzotrifluoride (ALDRICH) (3 g, 11.1 mmol), CuI (0.148 g, 0.78 mmol, 0.07 equiv), and Pd(PhCN)2CI2 (0.427 g, 1.1 mmol, 0.1 equiv) in dioxane (10 mL). The reaction mixture is stirred for 48 h at rt. Then, Pd(PhCN)2CI2 (0.100 g) is added. After stirring for additional 24 h, the reaction mixture is diluted with EtOAc and H2O and filtered through a pad of Celite. The filtrate is extracted with EtOAc. The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the crude material by silica gel column chromatography (CH2CI2/NH3(2 N in MeOH), 95:5) affords the title compound as a brown oil: ES-MS: 273.0 [M+H]+; single peak at tR= 3.06 min (System 1); Rf = 0.13 (CH2CI2/NH3(2 N in MeOH), 95:5).

Reference： [1]Patent: WO2006/108640,2006,A1 .Location in patent: Page/Page column 70

23
[ 367-67-9 ]
[ 4543-96-8 ]
[ 913173-48-5 ]

Yield	Reaction Conditions	Operation in experiment
	at 130℃; for 18h;	Step 5.2: N,N,N'-Trimethyl-N'-(4-nitro-2-trifluoromethyl-phenyl)-propane-1 ,3-diamine; A mixture of <strong>[367-67-9]2-bromo-5-nitrobenzotrifluoride</strong> (ALFA ACSAR) (1 g, 3.70 mmol) and N1N1N'- trimethylpropylene diamine (ALDRICH) (0.65 mL, 4.40 mmol, 1.2 equiv) is stirred in a sealed tube at 130 C for 18 h. The reaction mixture is allowed to cool to rt, triturated with Et2O and filtered. The filtrate is concentrated to give the title compound as a yellow oil. The residue in EPO <DP n="58"/>the filter is purified by silica column chromatography (CH2CI2/Me0H + 1 % NH3aq, 97:3) to afford an additional quantity of the title compound for a combined yield: ES-MS: 306.1 [M+H]+; Rf = 0.30 (CH2CI2/MeOH + 1 % NH3aq, 97:3).

Reference： [1]Patent: WO2006/108640,2006,A1 .Location in patent: Page/Page column 56-57

24
[ 367-67-9 ]
[ 107-18-6 ]
[ 924909-34-2 ]

Yield	Reaction Conditions	Operation in experiment
79%	With tetrabutylammomium bromide; triethylamine;palladium diacetate; In N,N-dimethyl-formamide; at 90℃; for 2h;	Example 191 1-[4-(3-Dimethylamino-propyl)-3-(trifluoromethyl)-phenyl]-3-[4-(6-methylamino)purin-9-yl]phenyl]urea (Table 2, Compound No.74) Step A Preparation of 3-(4-nitro-2-(trifluoromethyl)phenyl)-propionaldehyde [Show Image] In 3 mL of dimethylformamide, 50 mg (0.19 mmol) of 4-bromo-3-(trifluoromethyl)nitrobenzene was dissolved, and 33 mg (0.56 mmol) of allyl alcohol, 43 mg (0.19 mmol) of tetrabutylammonium bromide, 2.1 mg (5 mol%) of palladium acetate and 52 muL (0.37 mmol) of triethylamine were added thereto and the mixture solution was stirred in an argon atmosphere at 90C for two hours. The reaction solution was partitioned between water and ethyl acetate, and the organic layer was washed with a saturated sodium chloride solution and concentrated under reduced pressure. The product was purified by a silica gel column (n-hexane:ethyl acetate=5:1) to obtain 78 mg (79%) of a target product as a pale yellow oil.
69%	With tetrabutyl-ammonium chloride; triethylamine;palladium diacetate; In N,N-dimethyl-formamide; at 90℃; for 0.5h;	Preparation of 3-(4-nitro-2-(trifluoromethyl)phenyl)propionaldehyde 4-Bromo-3-(trifluoromethyl)nitrobenzene (2700 mg, 10 mmol) was dissolved in DMF (15 mL), and allyl alcohol (1750 mg, 30 mmol), tetrabutylammonium chloride (2780 mg, 10 mmol), palladium acetate (120 mg, 5 mol%), and triethylamine (3 mL, 21 mmol) were added thereto. The resulting mixture was stirred under argon atmosphere at 90C for 0.5 hours. The reaction solution was partitioned between water and ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography (n-hexane: ethyl acetate = 4:1) to give 3-(4-nitro-2-(trifluoromethyl)phenyl)propionaldehyde (1700 mg, 69%) as a light-yellow oil.

Reference： [1]Patent: EP1724258,2006,A1 .Location in patent: Page/Page column 173-174
[2]Patent: EP1921078,2008,A1 .Location in patent: Page/Page column 45

25
[ 367-67-9 ]
[ 140-88-5 ]
[ 863676-18-0 ]

Yield	Reaction Conditions	Operation in experiment
49%	With triethylamine;palladium diacetate; triphenylphosphine; In N,N-dimethyl-formamide; at 100℃; for 2h;	Example 250 N-Methyl-3-(4-{3-[4-(6-(methylamino)purin-9-yl)-phenyl]ureido}-2-(trifluoromethyl)phenyl)propionamide (Table 3, Compound No. 53) Step A Synthesis of (E)-3-(4-nitro-2-trifluoro-phenyl)-acrylic acid ethyl ester [Show Image] [Show Image] In 10 mL of dimethylformamide, 1.0 mg (3.7 mmol) of 4-bromo-3-(trifluoromethyl)nitrobenzene was dissolved, and 450 mg (4.5 mmol) of ethyl acrylate, 82 mg (0.37 mmol) of palladium acetate, 100 mg (0.37 mmol) of triphenyl-phosphine and 1.1 mL (7.9 mmol) of triethylamine were added thereto and the mixture solution was stirred in an argon atmosphere at 100C for two hours. The reaction solution was partitioned between water and ethyl acetate and the organic layer was washed with a saturated sodium chloride solution and concentrated under reduced pressure. The obtained residue was purified by a silica gel column (n-hexane:ethyl acetate=4:1) to obtain 500 mg (49%) of a target product as a pale yellow oil.

Reference： [1]Patent: EP1724258,2006,A1 .Location in patent: Page/Page column 204

26
[ 2510-22-7 ]
[ 367-67-9 ]
[ 863676-12-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In N,N-dimethyl-formamide; at 50℃;	Example 244 1-[4-(6-(Methylamino)purin-9-yl)phenyl]-3-[4-(2-pyridin-4-yl-ethyl)-3-(trifluoromethyl)phenyl]-urea (Table 3, Compound No. 47) Step A Preparation of 4-(4-nitro-2-(trifluoromethyl)phenylethynyl)pyridine [Show Image] In 20 mL of dimethylformamide, 1.0 g (3.7 mmol) of 4-bromo-3-(trifluoromethyl)nitrobenzene was dissolved, and 0.502 g (3.7 mmol) of 4-ethynylpyridine, 43 mg (3 mol%) of copper iodide, 78 mg (3 mol%) of dichlorobis(triphenylphosphine)palladium and 2.06 mL (0.56 mmol) of triethylamine were added thereto and the mixture solution was stirred overnight at 50C in an argon atmosphere. The reaction solution was partitioned between water and ethyl acetate and the organic layer was washed with a saturated sodium chloride solution and concentrated under reduced pressure. The residue was purified by a silica gel column (n-hexane:ethyl acetate=3:1) to obtain 1.3 g (quantitative) of a target product as an pale yellow oil. ESI (LC-MS positive mode) m/z 293 (M+H)

Reference： [1]Patent: EP1724258,2006,A1 .Location in patent: Page/Page column 198-199

27
bis(triphenylphosphone)palladium⁽¹¹⁾chloride [ No CAS ]
[ 367-67-9 ]
[ 54060-30-9 ]
3-amino-4'-nitro-2'-(trifluoromethyl)diphenylacetylene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(I) iodide; triethylamine; triphenylphosphine; In toluene;	EXAMPLE 11 Preparation of 3-Amino-4'-nitro-2'-(trifluoromethyl)diphenylacetylene A multinecked flask as described in Example 1 was charged with 10.0 g (0.037 mol) of <strong>[367-67-9]2-bromo-5-nitrobenzotrifluoride</strong>, 100 ml of dry triethylamine, 4.56 g (0.030 mol) of 3-aminophenyl-acetylene, 0.030 g (0.04 mmol) of bis(triphenylphosphone)palladium(11)chloride, 0.133 g (0.51 mmol) of triphenylphosphine, and 0.027 g (0.14 mmol) of cuprous iodide. The reaction mixture was heated at 60-65 C. for 18 hours at which point thin layer chromatography showed the reaction to be complete. After cooling to room temperature, the product mixture is diluted with 100 ml of 25% (v/v) toluene in ether and then filtered to remove the triethylamine hydrobromide by-product. The filtrate is concentrated on the rotary evaporator to give the product in quantitative yield as a bright yellow solid. The product can be further purified by recrystallization from aqueous ethanol.

Reference： [1]Patent: US5107026,1992,A

28
[ 367-67-9 ]
[ 641-98-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With 1,10-Phenanthroline; copper(I) bromide; In N,N-dimethyl-formamide; at 100℃; for 10h;Inert atmosphere;Catalytic behavior;	Under nitrogen protection, 270 g (1 mol) of <strong>[367-67-9]2-bromo-5-nitrobenzotrifluoride</strong> and 128 g (2 mol) of activated copper powder were sequentially added to a 2 L reaction flask equipped with a stirrer and a reflux condenser. 11.1 g (0.05 mol) of copper bromide, 19.8 g (0.1 mol) of phenanthroline, 1 L of anhydrous N,N-dimethylformamide, heated to 100 C, reacted for 10 h, and then filtered while hot. It was washed with methanol, concentrated to remove solvent and then recrystallized from 300 mL methanol. 136 g of a yellow solid were obtained in a yield of 85%.
71%	With copper; In N-methyl-acetamide;	EXAMPLE I Activated copper (45 g) was added to a solution of <strong>[367-67-9]2-bromo-5-nitro-benzotrifluoride</strong> (50 g) in 100 ml of dimethylformamide and the mixture refluxed for 5 hours. The cooled mixture was poured into excess water and the resulting brown precipitate collected by filtration, washed with water and dried. Chromatography over silica gel gave 25 g (71% yield) of STR6 2,2'-bis(trifluoromethyl)-4,4'-dinitro-1,1'-biphenyl, recrystallized as shiny yellow prisms from ether, m.p. 138-140 C.
	In N-methyl-acetamide;	Part A.--Preparation of 2,2'-bis(trifluoromethyl)-4,4'-dinitro-1,1'-biphenyl To a solution of <strong>[367-67-9]2-bromo-5-nitro-benzotrifluoride</strong> (50 grams) in 100 mls. of dimethylformamide were added 45 grams of activated copper and the mixture was refluxed for five hours. The reaction mixture was cooled and poured into excess water. The product, a brown precipitate, was filtered off, washed with water and dried. Chromatography over silica gel provided the product 2,2'-bis-(trifluoromethyl)-4,4'-dinitro-1,1'-biphenyl which was recrystallized from ether as shiny yellow prisms exhibiting a melting point of 140 C.

Reference： [1]Patent: CN109535005,2019,A .Location in patent: Page/Page column 5-7
[2]Polymer,2010,vol. 51,p. 4477 - 4483
[3]Patent: US4597891,1986,A
[4]Patent: US4503248,1985,A

29
[ 367-67-9 ]
[ 139301-27-2 ]
[ 875774-90-6 ]

Reference： [1]Patent: WO2006/13896,2006,A1 .Location in patent: Page/Page column 107

30
[ 367-67-9 ]
[ 927-74-2 ]
[ 924909-45-5 ]

Yield	Reaction Conditions	Operation in experiment
33%	With caesium carbonate;palladium diacetate; copper(l) iodide; XPhos; In 1,4-dioxane; at 80℃; for 10h;	Preparation of 4-(4-nitro-2-(trifluoromethyl)phenyl)but-3-yn-1-ol 4-Bromo-3-(trifluoromethyl)nitrobenzene (500 mg, 1.85 mmol) was dissolved in 1,4-dioxane (10 mL), and but-3-yn-1-ol (389 mg, 5.56 mmol), copper iodide (35 mg, 0.18 mmol), palladium acetate (21 mg, 5 mol%), 2-dicyclohexylphosphino-2',4',6'-triisopropyl bisphenyl (88 mg, 10 mol%), and cesium carbonate (1207 mg, 3.70 mmol) were added thereto. The resulting mixture was stirred under nitrogen atmosphere at 80C for 10 hours, and a saturated ammonium chloride aqueous solution was added thereto to quench the reaction. The reaction solution was extracted with ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography (n-hexane: ethyl acetate = 1:1) to give 4-(4-nitro-2-(trifluoromethyl)phenyl)but-3-yn-1-ol (160 mg, 33%) as a brown oil. 1H-NMR (270MHz, CDCl3) delta (ppm): 1.23 (2H, d, J=6.6Hz), 3.14 (2H, d, J=6.6Hz), 7.73 (1H, d, J=8.4Hz), 8.35 (1H, dd, J=2.3, 8.4Hz), 8.52 (1H, d, J=8.4Hz)

Reference： [1]Patent: EP1921078,2008,A1 .Location in patent: Page/Page column 51

31
[ 110-91-8 ]
[ 367-67-9 ]
[ 105316-06-1 ]

Yield	Reaction Conditions	Operation in experiment
	nickel; at 140℃; for 4h;	The title compound is synthesized by nucleophilic substitution reaction from1-brorno-4-nitro- 2-trifluoromethyl-benzene with the morpholine(140 C, 4 h) and further hydrogenolytic reduction of the nitro function to the amine by means of Raney nickel : m. p.: 149-151 C ; Rf (hexane/EtOAc 1: 1): 0.30 ; MS:[M+1] + =247. 1,'H-NMR (400 MHz, DMSO-d6) : 7.22 (d, 9 Hz,1 H), 6.77 (m, 2H), 5.37 (broad, 2H, NH2), 3.62 (m/broad, 4H,CH2), 2.67(m, broad 4H, CH2).

Reference： [1]Patent: WO2005/51366,2005,A2 .Location in patent: Page/Page column 109

32
[ 109-01-3 ]
[ 367-67-9 ]
4-(4-methyl-1-piperazinyl)-3-(trifluoromethyl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	nickel; at 140℃; for 4h;	The title compound is synthesized by nucleophilic substitution reaction from1-bromo-4-nitro-2-trifluoromethyl-benzene with the 1-methyl-piperazine (140 C, 4 h) and further hydrogenolytic reduction of the nitro function to the amine by means of Raney nickel : m. p.:121-123 C ; Rf(MeOH/CH2CI2 = 1: 5): 0.17 ; MS:[M+l = 260;'H-NMR (400 MHz, DMSO-d6) : 7.21 (d, 9 Hz, 1H), 6.74 (m, 2H), 5.35 (broad, 2H, NH2), 2.70 (broad, 4H,CH2), 2.36 (s/broad, 4H,CH2), 2.18 (s, 3H,CH3).

Reference： [1]Patent: WO2005/51366,2005,A2 .Location in patent: Page/Page column 104

33
[ 629-05-0 ]
[ 367-67-9 ]
[ 1007401-61-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In 1,4-dioxane; at 100℃; for 16h;	A mixture of 12 (l-Bromo-4-nitro-2-trifluoromethyl-benzene, 10.8g, 40 mmol), 13 (Oct-1-yne, 6.6g, 60mmol), CuI (1.52g, 8mmol), Pd(PPh3)2Cl2 (1.8g), Et3N(22ml, lOmmol), and dioxane (22ml) in a sealed tube under Ar is heated at 100 C for 16h. After cooling to_rt,_the_ mixtureTis filtered through celite, and washed with ethyl acetate. The filtrate is concentrated and purified by silica gel column chromatography (Ethyl acetate : Hexane = l:7)to give crude 14 as an oil.

Reference： [1]Patent: WO2008/147557,2008,A2 .Location in patent: Page/Page column 47

34
[ 58-08-2 ]
[ 367-67-9 ]
[ 1137486-83-9 ]

Reference： [1]Chemistry - A European Journal,2009,vol. 15,p. 1337 - 1340

35
[ 367-67-9 ]
[ 1186482-25-6 ]

Yield	Reaction Conditions	Operation in experiment
	Pd(PPh3)4; In tetrahydrofuran; (5-methylpyridin-2-yl)zinc(II) bromide;	Example 99 5-Methyl-2-(4-nitro-2-trifluoromethyl-phenyl)-pyridine A mixture of 1-bromo-4-nitro-2-trifluoromethyl-benzene (750 mg, 2.78 mmol) and Pd(PPh3)4 (160.7 mg, 0.14 mmol) was dissolved in 5-methyl-2-pyridylzinc bromide solution in THF (0.5M, 11.1 mL, 5.55 mmol) and heated under microwave irradiation at 130 C. for 10 minutes. The reaction was extracted with ethyl acetate (3*20 mL). The organic layers were combined, dried with magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography to give the desired product.

Reference： [1]Patent: US2009/226398,2009,A1

36
[ 367-67-9 ]
[ 1548-61-4 ]

Reference： [1]Angewandte Chemie - International Edition,2009,vol. 48,p. 8729 - 8732
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 3082 - 3093

37
(S)-2,2'-(bis(methoxymethoxy)-6,6'-dimethyl-1,1'-biphenyl-3,3'-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) [ No CAS ]
[ 367-67-9 ]
C₃₂H₂₆F₆N₂O₈ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2011,vol. 133,p. 6166 - 6169

38
[ 367-67-9 ]
[ 1294517-09-1 ]

Reference： [1]Journal of the American Chemical Society,2011,vol. 133,p. 6166 - 6169

39
[ 367-67-9 ]
[ 1294517-07-9 ]

Reference： [1]Journal of the American Chemical Society,2011,vol. 133,p. 6166 - 6169

40
[ 367-67-9 ]
[ 1314114-50-5 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 5403 - 5413

41
[ 367-67-9 ]
[ 71311-90-5 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 5403 - 5413

42
[ 367-67-9 ]
[ 135-19-3 ]
[ 71311-89-2 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 5403 - 5413

43
[ 367-67-9 ]
[ 1374358-47-0 ]

Reference： [1]Patent: WO2013/62892,2013,A1

44
[ 367-67-9 ]
[ 1431943-23-5 ]

Reference： [1]Patent: WO2013/62892,2013,A1

45
[ 367-67-9 ]
[ 24850-33-7 ]
4-nitro-1-(prop-2-en-1-yl)-2-(trifluoromethyl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 16h;Reflux; Inert atmosphere;	Step A: 4-Nitro-l-(prop-2-en-l-ylV2-(trifluoromethyl)benzeneA mixture of l-bromo-4-nitro-2-(trifluoromethyl)benzene (1.0 g, 3.7 mmol), Allyl Tri-n-butyltin (1.4 mL, 4.4 mmol), Lithium Chloride (470 mg, 1 1 mmol), and Palladium Tetrakis (210 mg, 0.18 mmol) in toluene (30 mL) was heated to reflux for 16 hours under nitrogen. TLC showed complete reaction at that point. The reaction was diluted with ethyl acetate, adsorbed onto silica gel, and purified by silica gel chromatography to afford the title product.

Reference： [1]Patent: WO2013/62892,2013,A1 .Location in patent: Page/Page column 56; 57

46
[ 367-67-9 ]
[ 1254056-48-8 ]

Reference： [1]Patent: WO2014/418,2014,A1
[2]Patent: US2015/197511,2015,A1

47
[ 367-67-9 ]
[ 1529769-18-3 ]

Reference： [1]Patent: WO2014/418,2014,A1
[2]Patent: US2015/197511,2015,A1

48
[ 367-67-9 ]
[ 375853-82-0 ]
[ 1232786-08-1 ]

Yield	Reaction Conditions	Operation in experiment
84%	With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; at 120℃;Inert atmosphere;	Add <strong>[367-67-9]2-bromo-5-nitrobenzotrifluoride</strong> (250 mg, 0.926 mmol) to dioxane (3 mL), then add tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-l(2H)- carboxylate (207 mg, 0.926 mmol), tetrakis(triphenylphosphine)palladium [Pd(PPh3)4, 35 mg, 0.03 mmol] and saturated sodium bicarbonate solution (1 mL) under nitrogen atmosphere. Stir the reaction mixture overnight at 120C. TLC (PE:EtOAc=5:l) shows the reaction is complete. Partition the mixture between EtOAc and water, dry the organic layer over sodium sulfate, filter and concentrate the filtrate under reduced pressure. Purify the residue by flash chromatography (silica gel, PE:EtOAc=5:l) to afford the desired product (289 mg, 84%).
84%	With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In 1,4-dioxane; at 120℃;Inert atmosphere;	Add <strong>[367-67-9]2-bromo-5-nitrobenzotrifluoride</strong> (250 mg, 0.926 mmol) to dioxane (3 mL), then add tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (207 mg, 0.926 mmol), tetrakis(triphenylphosphine)palladium [Pd(PPh3)4, 35 mg, 0.03 mmol] and saturated sodium bicarbonate solution (1 mL) under nitrogen atmosphere. Stir the reaction mixture overnight at 120 C. TLC (PE:EtOAc=5:1) shows the reaction is complete. Partition the mixture between EtOAc and water, dry the organic layer over sodium sulfate, filter and concentrate the filtrate under reduced pressure. Purify the residue by flash chromatography (silica gel, PE:EtOAc=5:1) to afford the desired product (289 mg, 84%).

Reference： [1]Patent: WO2014/418,2014,A1 .Location in patent: Page/Page column 37; 38
[2]Patent: US2015/197511,2015,A1 .Location in patent: Paragraph 0198; 0199

49
[ 367-67-9 ]
[ 75927-49-0 ]
4-nitro-2-(trifluoromethyl)-1-vinylbenzene [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 2303 - 2310

50
[ 367-67-9 ]
C₁₅H₁₈F₃NO₃ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 2303 - 2310

51
[ 367-67-9 ]
(R)-2-(4-nitro-2-(trifluoromethyl)phenethyl)hexan-1-ol [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 2303 - 2310

52
[ 367-67-9 ]
[ 108-93-0 ]
1-(cyclohexyloxy)-4-nitro-2-(trifluoromethyl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With caesium carbonate; In N,N-dimethyl-formamide; at 60℃; for 16h;Inert atmosphere;	Cyclohexanol (0.371 g, 3.70 mmol) and cesium carbonate (1.81 g, 5.55 mmol) were stirred indry N,N-dimethylformamide (DMF) (4 mL) under nitrogen atmosphere. To this added <strong>[367-67-9]1-bromo-4-nitro-2-(trifluoromethyl)benzene</strong> (0.5 g, 1.852 mmol) and the reaction mixture washeated to 60 C for 16 hours. The reaction mixture was quenched with water (5 mL) and extracted with ethyl acetate (20 mL). The organic layer was washed with water (2 X 10 mL) and brine (10 mL), dried over sodium sulphate and concentrated to obtain the title compound. Yield: 200 mg (20.0 %).

Reference： [1]Patent: WO2015/145371,2015,A1 .Location in patent: Page/Page column 41

53
[ 367-67-9 ]
[ 108-93-0 ]
[ 946730-93-4 ]

Reference： [1]Patent: WO2015/145371,2015,A1

54
[ 367-67-9 ]
8-(4-nitro-2-(trifluoromethyl)phenyl)-1,4-dioxaspiro[4.5]dec-7-ene [ No CAS ]

Reference： [1]Patent: WO2015/145371,2015,A1

55
[ 367-67-9 ]
4’-nitro-2’-(trifluoromethyl)-5,6-dihydro-[1,1‘-biphenyl]-4(3H)-one [ No CAS ]

Reference： [1]Patent: WO2015/145371,2015,A1

56
[ 367-67-9 ]
4’-amino-2’-(trifluoromethyl)-5,6-dihydro-[1,1‘-biphenyl]-4(3H)-one [ No CAS ]

Reference： [1]Patent: WO2015/145371,2015,A1

57
[ 367-67-9 ]
[ 73183-34-3 ]
4,4,5,5-tetramethyl-2-(4-nitro-2-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; for 16h;Inert atmosphere; Reflux;	To a solution of <strong>[367-67-9]1-bromo-4-nitro-2-(trifluoromethyl)benzene</strong> (5.0 g, 18.52 mmol) and4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1 ,3,2-dioxaborolane) (4.70 g, 18.52 mmol) in dioxane(50 mL), nitrogen was purged for 15 minutes and added potassium acetate (2.73 g, 27.8mmol), [1,1 -bis(diphenylphosphino)ferrocene] dichloro palladium (I) complex with DCM(0.756 g, 0.926 mmol). The reaction mixture was refluxed for 16 hours and cooled thereaction mixture to RT. The reaction mixture was filtered through celite, filtrate wasconcentrated and purified by column chromatography (silica gel, hexane and ethyl acetate) to obtain the title compound.Yield: 3.2 g (54 %); 1H NMR (CDC13, 300 MHz): oe ppm 1.27 (s, 12H), 7.97 (d, J=9.OHz, 1H), 8.28 (dd, J1 & J2=3.OHz, 1H), 8.58 (d, J=3.OHz, 1H); Mass (ESI): mlz 316.1 [M-H] .

Reference： [1]Patent: WO2015/145371,2015,A1 .Location in patent: Page/Page column 46

58
[ 367-67-9 ]
[ 536-74-3 ]
4-nitro-1-(phenylethynyl)-2-(trifluoromethyl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine; at 60℃; for 6h;	In a 250mL three-necked bottle equipped with a mechanical stirrer, thermometer, and nitrogen inletAdd 5.4129g (53mmol) of phenylacetylene, 123mg (0.35mmol) of PdCl2 (PPh3) 2, 184mg (0.70mmol) ofTriphenylphosphine, 200mg (1.05mmol)IodideAnd 150ml of anhydrous triethylamine, heated to 60 after adding 14.310g (53mmol) of <strong>[367-67-9]2-bromo-5-nitrotrifluorotoluene</strong>, maintained at this temperature for 6 hours. Triethylamine was distilled off under reduced pressure, 100 ml of ether was added to the system, the filtrate was collected by filtration, and the solvent was removed by rotary evaporation to obtain a yellow solid, which was recrystallized from ethanolAfter that, 3-trifluoromethyl-4-phenylethynylnitrobenzene is obtained.

Reference： [1]Chemistry Letters,2016,vol. 45,p. 75 - 77
[2]Patent: CN105130819,2018,B .Location in patent: Paragraph 0066

59
[ 367-67-9 ]
4-nitro-3-(trifluoromethyl)benzil [ No CAS ]

Reference： [1]Chemistry Letters,2016,vol. 45,p. 75 - 77
[2]Patent: CN105130819,2018,B

60
[ 367-67-9 ]
1,4-bis(4-phenylglyoxaloyl-3-(trifluoromethyl)phenoxy)benzene [ No CAS ]

Reference： [1]Chemistry Letters,2016,vol. 45,p. 75 - 77
[2]Chemistry Letters,2016,vol. 45,p. 75 - 77
[3]Patent: CN105130819,2018,B

61
[ 367-67-9 ]
[ 32547-85-6 ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 3082 - 3093

62
[ 367-67-9 ]
4-(4-((4-nitro-2-(trifluoromethyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-2-(trifluoromethyl)benzonitrile [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 3082 - 3093

63
[ 367-67-9 ]
4-((4-nitro-2-(trifluoromethyl)phenoxy)methyl)-1-(3-(trifluoromethyl)phenyl)-1H-1,2,3-triazole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 3082 - 3093

64
[ 367-67-9 ]
4-(5-iodo-4-((4-nitro-2-(trifluoromethyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-2-(trifluoromethyl)benzonitrile [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 3082 - 3093

Yield	Reaction Conditions	Operation in experiment
92%	With bromine; dibromoisocyanuric acid; In dichloromethane; at 60℃; for 24h;UV-irradiation;	General procedure: EXAMPLE 6 Bromoisocyanurate induced radical bromodecarboxylation of (0335) arenecarboxylic acids bromoisocyanurate (0336) ArCO H ArBr (0337) 2 hv (0338) [00139] A mixture of arenecarboxylic acid ArC02H (1 mmol), bromoisocyanurate, additive and solvent (10 mL) was stirred under fluorescent room light (FL) or warm-white 3 W LED (LL) irradiation (hv). The reaction mixture washed with 1 M aq Na2S03, dried over Na2S04, filtered through short neutral alumina pad and concentrated in vacuo to yield crude bromoarene ArBr. Optionally, the crude bromide was purified by chromatography on silica gel. The results are presented in Table 5.

66
[ 88-17-5 ]
[ 367-67-9 ]

Reference： [1]Patent: CN106905104,2017,A

67
[ 367-67-9 ]
[ 287944-16-5 ]
C₁₂H₁₀F₃NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
900 mg	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 0.166667h;Inert atmosphere; Microwave irradiation;	A solution of 2-bromo-5-nitrobenzotrifluride (1.00 g, 3.704 mmol) and 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester (1 .01 g, 4.82 mmol) in a mixture of 1 ,4-dioxane(15.28 mL) and distilled water (2.59 mL) was treated with K2C03 (2.36 g, 11.11 mmol)and purged with N2. Dichloro [1,1?-bis(diphenylphosphino)ferrocene]palladium II,DCM adduct (303.20 mg, 370.36 jimol) was then added and the reaction mixture was purged again with N2 and stirred at 120 C using one single mode microwave (Biotage Initiator EXP 60) with a power output ranging from 0 to 400 W for 10 minutes [fixed hold time]. Then, water was added. The aqueous layer was extracted twice with DCM,dried over MgSO4, filtered and evaporated. The residue was purified by columnchromatography on silica gel (Irregular SiOH, 40jim, mobile phase DCM, 100%DCM). The pure fractions were combined and the solvent was evaporated to give 900mg of intermediate 129.

Reference： [1]Patent: WO2017/125530,2017,A1 .Location in patent: Page/Page column 267

68
[ 367-67-9 ]
[ 287944-16-5 ]
C₁₂H₁₄F₃NO [ No CAS ]

Reference： [1]Patent: WO2017/125530,2017,A1

69
[ 367-67-9 ]
1-propyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)pyridin-2(1H)-one [ No CAS ]
5-(4-(4-nitro-2-(trifluoromethyl)phenyl)-1H-pyrazol-1-yl)-1-propylpyridin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 100℃; for 0.75h;Inert atmosphere; Microwave irradiation;	[00308] A micro wave vial was charged with 1-propyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)pyridin-2(1H)-one (0.200 g, 0.6 mmol), <strong>[367-67-9]2-bromo-5-nitrobenzotrifluoride</strong> (0.180 g, 0.8 mmol), and dioxan (8 mL) and water (2 mL) and the flask was degassed and flushed with argon. PdCl2(dppf) (0.050 g, 0.1 mmol) was added and the reaction flask was again degassed and flushed with argon. The reaction mixture was then heated to 100C in a microwave for 45 minutes. The reaction was cooled to room temperature and quenched with sat. NaHC03 and extracted with ethyl acetate (3X50 mL). The combined organics were washed with water, brine and dried over MgS04. The solvents were evaporated to dryness and the residue purified by flash chromatography (silica gel, 0-60% ethyl acetates in hexanes) to afford the product as yellow solid (170 mg, 71%). LC/MS: [M+l]+, 393.3; 1H MR (300 MHz, CDC13): delta 8.66 (d, J=2.4 Hz, IH), 8.43 (dd, J=9.0 and 2.4 Hz, IH), 7.91 (s, IH), 7.85 (s, IH), 7.81 (d, J=3.0 Hz, IH), 7.70-7.62 (m, 2H), 6.70 (d, J=9.3 Hz, IH), 3.98 (t, J=7.5 Hz, 2H), 1.90-1.81 (m, 2H), 1.02 (t, J=6.9 Hz, 3H).

Reference： [1]Patent: WO2017/190086,2017,A1 .Location in patent: Paragraph 00308

70
[ 367-67-9 ]
4-bromo-N-ethylpyridin-2-amine [ No CAS ]
N-ethyl-4-(4-nitro-2-(trifluoromethyl)phenyl)pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%		General procedure: To a mixture of bis(pinacolato)diboron (2.13g, 8.4mmol), Pd2dba3 (0.22 g, 0.02 mmol, 3%), XPhos(0.61, 1.28mmol, 16%), 12a(1.60g, 8mmol)and anhydrous KOAc (1.88g, 19.2mmol) was added anhydrous1,4-dioxane(30ml), and the reaction mixture was refluxed for 12 h under argon; After the solution was cooled to room temperature, 1-bromo-2-methyl-4-nitrobenzene13a(1.73g, 8mmol), Pd2dba3 (0.22 g, 0.02 mmol, 3%), K3PO4(4.24g, 20mmol), H2O(10ml)was added to the above reaction solution and then refluxed for another 12 h under argon. At the end of the reaction, the mixture was partitioned between water and ethyl acetate.The organic layer was separated, and concentrated, and then the crude product was purified by silica gel column chromatography using a mixture solvent of petroleum ether: ethylacetate (5:1),to give 14a.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 144,p. 517 - 528

71
[ 367-67-9 ]
4-bromo-N-propylpyridin-2-amine [ No CAS ]
4-(4-nitro-2-(trifluoromethyl)phenyl)-N-propylpyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%		General procedure: To a mixture of bis(pinacolato)diboron (2.13g, 8.4mmol), Pd2dba3 (0.22 g, 0.02 mmol, 3%), XPhos(0.61, 1.28mmol, 16%), 12a(1.60g, 8mmol)and anhydrous KOAc (1.88g, 19.2mmol) was added anhydrous1,4-dioxane(30ml), and the reaction mixture was refluxed for 12 h under argon; After the solution was cooled to room temperature, 1-bromo-2-methyl-4-nitrobenzene13a(1.73g, 8mmol), Pd2dba3 (0.22 g, 0.02 mmol, 3%), K3PO4(4.24g, 20mmol), H2O(10ml)was added to the above reaction solution and then refluxed for another 12 h under argon. At the end of the reaction, the mixture was partitioned between water and ethyl acetate.The organic layer was separated, and concentrated, and then the crude product was purified by silica gel column chromatography using a mixture solvent of petroleum ether: ethylacetate (5:1),to give 14a.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 144,p. 517 - 528

72
[ 367-67-9 ]
4-bromo-N-(cyclopropylmethyl)pyridin-2-amine [ No CAS ]
N-(cyclopropylmethyl)-4-(4-nitro-2-(trifluoromethyl)phenyl)pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%		General procedure: To a mixture of bis(pinacolato)diboron (2.13g, 8.4mmol), Pd2dba3 (0.22 g, 0.02 mmol, 3%), XPhos(0.61, 1.28mmol, 16%), 12a(1.60g, 8mmol)and anhydrous KOAc (1.88g, 19.2mmol) was added anhydrous1,4-dioxane(30ml), and the reaction mixture was refluxed for 12 h under argon; After the solution was cooled to room temperature, 1-bromo-2-methyl-4-nitrobenzene13a(1.73g, 8mmol), Pd2dba3 (0.22 g, 0.02 mmol, 3%), K3PO4(4.24g, 20mmol), H2O(10ml)was added to the above reaction solution and then refluxed for another 12 h under argon. At the end of the reaction, the mixture was partitioned between water and ethyl acetate.The organic layer was separated, and concentrated, and then the crude product was purified by silica gel column chromatography using a mixture solvent of petroleum ether: ethylacetate (5:1),to give 14a.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 144,p. 517 - 528

73
[ 367-67-9 ]
5-bromo-2-nitro-4-(trifluoromethyl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With tert.-butylhydroperoxide; ammonium hydroxide; potassium tert-butylate; In tetrahydrofuran; at -60 - -30℃; for 0.5h;	Potassium tert-butoxide (1.68 g, 14.97 mmol) was added in portions to a -60 C solution of liquid ammonia (20 mL). A solution of tert-butyl hydroperoxide (590 mg, 6.55 mmol) and l-bromo-4-nitro-2-(trifluoromethyl)benzene (1.61 g, 5.96 mmol) in tetrahydrofuran (6 mL) was added, and the resulting solution was stirred for 30 min at -30 C. The reaction was then quenched by the addition of 50 mL of saturated aqueous ammonium chloride, and the resulting mixture was extracted with 3x50 mL of ethyl acetate. The combined organic layers were concentrated under vacuum. The crude product was purified by recrystallization from petroleum ether/ethyl acetate (10: 1) to give 5-bromo-2-nitro-4-(trifluoromethyl)phenol (1.5 g, 88%) as a yellow solid. MS: (ESI, m/z): 284[M-H]".

Reference： [1]Patent: WO2018/75959,2018,A1 .Location in patent: Paragraph 0410-0411

74
[ 367-67-9 ]
2-amino-5-bromo-4-(trifluoromethyl)phenol [ No CAS ]