[ CAS No. 876322-58-6 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

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

2D 3D

Structure of 876322-58-6 * Storage: {[proInfo.prStorage]}

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

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 [ 876322-58-6 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 876322-58-6 ]

SDS Specification

Alternatived Products of [ 876322-58-6 ]

Product Details of [ 876322-58-6 ]

CAS No. :	876322-58-6	MDL No. :
Formula :	C₂₁H₂₃BF₃NO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	405.22	Pubchem ID :	-
Synonyms :

Safety of [ 876322-58-6 ]

Signal Word:	Warning	Class:
Precautionary Statements:	P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330	UN#:
Hazard Statements:	H302-H315-H319	Packing Group:
GHS Pictogram:

Application In Synthesis of [ 876322-58-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 876322-58-6 ]

[ 876322-58-6 ] Synthesis Path-Downstream 1~12

1
[ 876322-59-7 ]
[ 73183-34-3 ]
[ 876322-58-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate In tetrahydrofuran for 18h; Heating / reflux;	1.1 N-(3-Isoquinolin-7-yl-4-methyl-phenyl)-3-trifluoromethyl-benzamide Step 1.1: N-[4-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-3-trifluoromethyl benzamide Nitrogen is bubbled through a mixture of 5.0 g (14 mmol) N-(3-bromo-4-methyl-phenyl)-3-trifluoromethyl-benzamide and 3.42 g (34.5 mmol) potassium acetate in 50 mL of THF for about 20 minutes. After the addition of 4.06 mg (16 mmol) bis-(pinacolato)-diboron, 6 mol-% of 1,1'-bis(diphenylphospino)ferrocene-palladium dichloride (700 mg, 0.8 mmol) is added and the resulting mixture heated under reflux for 18 h. The reaction mixture is then cooled to RT and diluted with ethyl acetate. After washing the mixture with conc. Sodium chloride solution, the ethyl acetate phase is dried with sodium sulphate and evaporated. The crude product is purified by flash chromatography using dichloromethane as solvent. The title compound is obtained as a colourless solid; m.p. 148-152° C.; Rf (dichloromethane)=0.36; HPLC tR=4.82 min; MS-ES+: (M+H)+=406.
	With potassium acetate In tetrahydrofuran for 18h; Heating / reflux;	1.1 Nitrogen is bubbled through a mixture of 5.0 g (14 mmol) N-(3-bromo-4- methyl-phenyl)-3-trifluoromethyl-benzamide and 3.42 g (34.5 mmol) potassium acetate in 50 mL of THF for about 20 minutes. After the addition of 4.06 mg (16 mmol) bis-(pinacolato)-diboron, 6 mol-% of l,l '-bis(diphenylphospino)ferrocene- palladium dichloride (700 mg, 0.8 mmol) is added and the resulting mixture heated under reflux for 18 h. The reaction mixture is then cooled to RT and diluted with ethyl acetate. After washing the mixture with cone. Sodium chloride solution, the ethyl acetate phase is dried with sodium sulphate and evaporated. The crude product is purified by flash chromatography using dichloromethane as solvent. The title compound is obtained as a colorless solid; m.p. 148-152 0C; Rf (dichloromethane) = 0.36; HPLC tR = 4.82 min; MS-ES+: (M+H)+ = 406.

Reference： [1]Current Patent Assignee: MARTINY BARON; S H ENG; CARAVATTI; IMBACH; NOVARTIS AG; PEREZ; Novartis (w/o Sandoz); FURET - US2006/35897, 2006, A1 Location in patent: Page/Page column 19
[2]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2008/8821, 2008, A2 Location in patent: Page/Page column 34

2
[ 876322-58-6 ]
[ 89892-21-7 ]
N-(4-methyl-3-quinazolin-6-yl-phenyl)-3-trifluoromethyl-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; triphenylphosphine;palladium diacetate; In ethanol; toluene; at 90℃; for 8h;	Example 2 N-(4-Methyl-3-quinazolin-6-yl-phenyl)-3-trifluoromethyl-benzamide A mixture of N-[4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-3-tri-fluoromethyl-benzamide (0.456 g, 1.125 mmol) and <strong>[89892-21-7]6-bromo-quinazoline</strong> (0.157 g, 0.75 mmol) in 3 mL of toluene and 0.375 mL of ethanol is treated with 0.75 mL of a 2 molar solution of sodium carbonate and the resulting mixture is degassed by bubbling nitrogen through the mixture for 5 min. After the addition of palladium acetate (0.0075 g, 0.034 mmol) and triphenylphosphine (0.0293 g, 0.117 mmol), the mixture is stirred at 90 C. for 2 h. The same amount of palladium acetate and triphenylphosphine is added again and the mixture stirred for 6 h at 90 C. The reaction mixture is cooled and added to 10 mL ethyl acetate and 4 mL of water. The bi-phasic mixture is filtered through Hyflo Super Cele (Fluka, Buchs, Switzerland), the organic layer separated, dried with sodium sulphate and evaporated to leave a brown resin. The crude product is purified by chromatography using a 40 g silica gel column on a Combi-Flash Companion (Isco Inc.) apparatus. A gradient of dichloromethane/methanol 100:1 to 100:15 is used. Enriched fractions are re-chromatographed on the same system using a 40 g silica gel column and tert-butyl-methylether as solvent. Pure fractions are pooled and evaporated to give the title compound as a tan foam; Rf (dichloromethane/ethanol 9:1)=0.56; HPLC tR=3.23 min; MS-ES+: (M+H)+=408.
	With sodium carbonate;palladium diacetate; triphenylphosphine; In ethanol; water; toluene; at 90℃; for 8h;	A mixture of N-[4-methyl-3-(4,4,5,5-tetramethyl-[l ,3,2]dioxaborolan-2-yl)- phenyl]-3-trifluoromethyl-benzamide (0.456 g, 1.125 mmol) and <strong>[89892-21-7]6-bromo-quinazoline</strong> (0.157 g, 0.75 mmol) in 3 mL of toluene and 0.375 mL of ethanol is treated with 0.75 mL of a 2 molar solution of sodium carbonate and the resulting mixture is degassed by bubbling nitrogen through the mixture for 5 min. After the addition of palladium acetate (0.0075 g, 0.034 mmol) and triphenylphosphine (0.0293 g, 0.117 mmol), the mixture is stirred at 90 0C for 2 h. The same amount of palladium acetate and triphenylphosphine is added again and the mixture stirred for 6 h at 90 0C. The reaction mixture is cooled and added to 10 mL ethyl acetate and 4 mL of water. The bi -phasic mixture is filtered through Hyflo Super Cel (Fluka, Buchs, Switzerland), the organic layer separated, dried with sodium sulphate and evaporated to leave a brown resin. The crude product is purified by chromatography using a 40 g silica gel column on a Combi-Flash Companion (Isco Inc.) apparatus. A gradient of dichloromethane/methanol 100:1 to 100:15 is used. Enriched fractions are re-chromatographed on the same system using a 40 g silica gel column and tert-butyl-methylether as solvent. Pure fractions are pooled and evaporated to give the title compound as a tan foam; Rf (dichloromethane/ethanol 9:1) = 0.56; HPLC tR = 3.23 min; MS-ES+: (M+H)+ = 408.

Reference： [1]Patent: US2006/35897,2006,A1 .Location in patent: Page/Page column 20
[2]Patent: WO2008/8821,2008,A2 .Location in patent: Page/Page column 35; 36

3
[ 876322-58-6 ]
[ 404827-77-6 ]
[ 1238376-14-1 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 120℃; for 0.25h;Inert atmosphere; Microwave irradiation;	Example 121; N-[3-(3-amino-1H-indazol-6-yl)-4-methylphenyl]-3-(trifluoromethyl)benzamide (Scheme 3); A solution of N-[4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3-(trifluoromethyl)benzamide (intermediate 3.2.1, 40 mg, 0.1 mmol) and <strong>[404827-77-6]6-bromo-1H-indazol-3-amine</strong> (23 mg, 0.11 mmol) in DMF (0.5 mL) and 1M cesium carbonate (0.25 mL) is degassed with nitrogen for 2 min. 1,1'-bis(diphenylphosphino)ferrocene-palladium dichloride, DCM complex (4 mg, 0.005 mmol) was added and the reaction mixture was irradiated at 120 C. in a microwave for 15 min. The reaction mixture was filtered and purified by reverse phase preparative HPLC to provide N-[3-(3-amino-1H-indazol-6-yl)-4-methylphenyl]-3-(trifluoromethyl)benzamide as a TFA salt. MS M+1=411.

Reference： [1]Patent: US2010/197688,2010,A1 .Location in patent: Page/Page column 50

4
[ 882670-69-1 ]
[ 2251-65-2 ]
[ 876322-58-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	In tetrahydrofuran; for 2.5h;	To a solution of <strong>[882670-69-1]4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline</strong> (9, 5.0 g, 21.5 mmol) in 200 mL THF was added 3-(trifluoromethyl)benzoyl chloride (3.2 mL, 21.5 mmol). After 2.5 h the solution was concentrated in vacuo to give 11 as a white solid (8.7 g, 99 %). LC/MS (m/z): 406.2 (MH+), Rt: 1.24 min.
93%	In tetrahydrofuran; at 0 - 20℃; for 3h;	To a solution of <strong>[882670-69-1]4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline</strong> (1.0 equiv.) in THF (0.1 M) at 0 C. was added 3-trifluoromethylbenzoylchloride (1.0 equiv.) and the reaction was stirred at room temperature for 3 h. The solution was concentrated and dried under vacuo to give N-(4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(trifluoromethyl)benzamide as a tan solid in 96% yield. LCMS (m/z) (M+H)=406.2, Rt=1.24 min.
91%	With triethylamine; In dichloromethane; at 0℃; for 0.166667h;	Reference Example 5 N-[4-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)]-3-(trifluoromethyl)benzamide (Compound A5) Compound A4 (0.50 g, 2.04 mmol) was dissolved in dichloromethane (21 mL), followed by cooling to 0C, then triethylamine (0.387 mL, 2.78 mmol), and 3-trifluoromethylbenzoyl chloride (0.339 mL, 2.25 mmol) were added thereto, followed by stirring for 10 minutes. Water was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with brine, followed by drying over anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated to obtain Compound A5 (0.80 g, 91%). 1H NMR (300 MHz, CDCl3) delta (ppm) 1.35 (s, 12H), 2.53 (s, 3H), 7.22 (d, J = 6.6 Hz, 1H), 7.58-7.68 (m, 2H) 7.74-7.84 (m, 2H), 7.93-8.00 (m, 1H), 8.05 (d, J = 7.5 Hz, 1H) 8.12 (s, 1H).

	With triethylamine; In dichloromethane; at 3℃; for 0.166667h;Inert atmosphere;	Illustrative synthesis of Intermediate Gen-5-b: N-[4-Methyl-3-(4,4,5,5-tetramethyl- [l,3,2]dioxaborolan-2-yl)-phenyl]-3-trifluoromethyl-benzamide A solution of Intermediate Gen-3-a (293 g, 1.26 mol, 1.0 eq.) in DCM (3 L) under nitrogen is cooled to 3C, then TEA (193 mL, 1.38 mol, 1.1 eq.) followed by Gen-l-e (150 mL, 1.0 mol, 0.8 eq.) are added dropwise. Then Gen-l-e (9.5 mL, 0.06 mol, 0.05 eq.) is added dropwise and the reaction is left to stir 10 min. The reaction mixture is quenched with water (1.5 L) and diluted with DCM (2 L). The layers are separated and the organic layer is dried over Na2S04, filtered and evaporated in vacuo. The majority of the solvant is removed and cyclohexane (3.0 L) is added. The mixture is stirred at room temperature for few minutes, the resulting solid is separated by filtration and washed with cyclohexane and dried to afford Intermediate Gen-5-b. LCMS: MW (calcd): 405; m/z MW (obsd): 406 (M+H).
	With triethylamine; In dichloromethane; at 3℃; for 0.166667h;Inert atmosphere;	A solution of Intermediate Gen-3-a (293 g, 1.26 mol, 1.0 eq.) in DCM (3 L) under nitrogen is cooled to 3 C., then TEA (193 mL, 1.38 mol, 1.1 eq.) followed by Gen-1-e (150 mL, 1.0 mol, 0.8 eq.) are added dropwise. Then Gen-1-e (9.5 mL, 0.06 mol, 0.05 eq.) is added dropwise and the reaction is left to stir 10 min. The reaction mixture is quenched with water (1.5 L) and diluted with DCM (2 L). The layers are separated and the organic layer is dried over Na2SO4, filtered and evaporated in vacuo. The majority of the solvent is removed and cyclohexane (3.0 L) is added. The mixture is stirred at room temperature for few minutes, the resulting solid is separated by filtration and washed with cyclohexane and dried to afford Intermediate Gen-5-b. LCMS: MW (calcd): 405; m/z MW (obsd): 406 (M+H). . 1H NMR (300 MHz, CDCl3-d) delta ppm 8.13 (1H, s), 8.05 (1H, bd), 8.00-7.9 (2H, m), 7.80 (1H, bd), 7.71 (1H, d), 7.61 (1H, t), 7.20 (1H, d), 2.54 (3H, s), 1.36 (12H, s).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 5221 - 5224
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 4869 - 4881
[3]Patent: US2014/275003,2014,A1 .Location in patent: Paragraph 0156; 0157
[4]Patent: EP2269993,2011,A1 .Location in patent: Page/Page column 52
[5]Patent: WO2015/24905,2015,A1 .Location in patent: Paragraph 00222-00223; 00347-00348
[6]Patent: US2015/80391,2015,A1 .Location in patent: Paragraph 0450; 0451; 0452; 0658; 0659; 0660

5
[ 876322-58-6 ]
[ 933728-73-5 ]
N-(4-methyl-3-(2-morpholinothiazol-5-yl)phenyl)-3-(trifluoromethyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,2-dimethoxyethane at 108℃; for 0.216667h; Microwave irradiation;	198.2 N-(4-methyl-3-(2-morpholinothiazol-5-yl)phenyl)-3-(trifluoromethyl)benzamide Step 2: A mixture of 4-(5-bromothiazol-2-yl)morpholine (1.0 equiv.), N-(4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(trifluoromethyl)benzamide (1.2 equiv.), sodium carbonate (2 M, 8 equiv.) and PdCl2(dppf) (0.5 equiv.) in DME (0.1 M) were heated to 108° C. for 13 min in the microwave. After removing the DME soluble portion and concentrating, the resulting solid was partitioned between EtOAc and water. The organic phase was washed with brine and then dried over magnesium sulfate. After concentration, the crude material was purified via preparative reverse phase HPLC. Upon lyophilization of the pure fractions, N-(4-methyl-3-(2-morpholinothiazol-5-yl)phenyl)-3-(trifluoromethyl)benzamide was isolated as the TFA salt in 15% yield. 1H NMR (400 MHz, ) δ ppm 2.36 (s, 3H) 3.40-3.43 (m, 4H) 3.70-3.74 (m, 4H) 7.22-7.33 (m, 2H) 7.63 (dd, J=8.22, 1.96 Hz, 1H) 7.72-7.84 (m, 2H) 7.95 (d, J=7.43 Hz, 1H) 8.19-8.33 (m, 2H) 10.45 (s, 1H). LCMS (m/z) (M+H)=448.2, Rt=0.83 min.

6
[ 876322-58-6 ]
[ 1040377-12-5 ]
N-(4-methyl-3-(2-morpholinopyridin-4-yl)phenyl)-3-(trifluoromethyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate In 1,2-dimethoxyethane; water at 120℃; for 0.333333h; Microwave irradiation;
16%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate In 1,2-dimethoxyethane at 120℃; for 0.333333h; Microwave irradiation;	62 Synthesis of N-(4-methyl-3-(2-morpholinopyridin-4-yl)phenyl)-3-(trifluoromethyl)benzamide. Synthesis of N-(4-methyl-3-(2-morpholinopyridin-4-yl)phenyl)-3-(trifluoromethyl)benzamide. To a solution of 4-(4-bromopyridin-2-yl)morpholine (1.0 equiv.) and Intermediate A (1.2 equiv.) in DME and 2M sodium carbonate (3:1, 0.08 M) was added PdCl2(dppf)-DCM adduct (0.1 equiv.) in a microwave vial equipped with a stir bar. The reaction was heated to 120° C. for 20 min in the microwave. The reaction was quenched with water and extracted with ethyl acetate. The combined organic phase was dried with sodium sulfate, filtered and concentrated. The crude material was purified via preparative reverse phase HPLC. Upon lyophilization of the pure fractions, N-(4-methyl-3-(2-morpholinopyridin-4-yl)phenyl)-3-(trifluoromethyl)benzamide was isolated as the TFA salt in 16% yield.LCMS (m/z) (M+H)=442.3, Rt=0.76 min. 1H NMR (400 MHz, ) δ ppm 2.25 (s, 3H) 3.44-3.59 (m, 5H) 3.64-3.87 (m, 22H) 6.82 (d, J=5.48 Hz, 1H) 7.00 (s, 1H) 7.27-7.41 (m, 1H) 7.67-7.82 (m, 3H) 7.90-8.03 (m, 1H) 8.17 (d, J=5.48 Hz, 1H) 8.26 (d, J=7.83 Hz, 1H) 8.30 (s, 1H) 10.40-10.61 (m, 1H).

Reference： [1]Nishiguchi, Gisele A.; Rico, Alice; Tanner, Huw; Aversa, Robert J.; Taft, Benjamin R.; Subramanian, Sharadha; Setti, Lina; Burger, Matthew T.; Wan, Lifeng; Tamez, Victoriano; Smith, Aaron; Lou, Yan; Barsanti, Paul A.; Appleton, Brent A.; Mamo, Mulugeta; Tandeske, Laura; Dix, Ina; Tellew, John E.; Huang, Shenlin; Mathews Griner, Lesley A.; Cooke, Vesselina G.; Van Abbema, Anne; Merritt, Hanne; Ma, Sylvia; Gampa, Kalyani; Feng, Fei; Yuan, Jing; Wang, Yingyun; Haling, Jacob R.; Vaziri, Sepideh; Hekmat-Nejad, Mohammad; Jansen, Johanna M.; Polyakov, Valery; Zang, Richard; Sethuraman, Vijay; Amiri, Payman; Singh, Mallika; Lees, Emma; Shao, Wenlin; Stuart, Darrin D.; Dillon, Michael P.; Ramurthy, Savithri [Journal of Medicinal Chemistry, 2017, vol. 60, # 12, p. 4869 - 4881]
[2]Current Patent Assignee: NOVARTIS AG; Barsanti, Paul A.; Burger, Matthew; Lou, Yan; Nishiguchi, Gisele; Polyakov, Valery; Ramurthy, Savithri; Rico, Alice; Setti, Lina; Smith, Aaron; Taft, Benjamin; Tanner, Huw; DiPesa, Alan; Yusuff, Naeem - US2014/275003, 2014, A1 Location in patent: Paragraph 0392; 0399

7
[ 876322-58-6 ]
[ 401816-16-8 ]
N-(3-(2,6-difluoropyridin-4-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; at 80℃; for 18h;	Synthesis of N-(3-(2,6-difluoropyridin-4-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide To a solution of <strong>[401816-16-8](2,6-difluoropyridin-4-yl)boronic acid</strong> (1.5 equiv.) and Intermediate X (1.0 equiv.) in DME and 2M sodium carbonate (3:1, 0.2 M) was added PdCl2(dppf)-DCM adduct (0.1 equiv.) in a vial equipped with a stir bar. The reaction was heated to 80 C. for 18 hours. The reaction was quenched with water and extracted with ethyl acetate. The combined organic phase was dried with sodium sulfate, filtered and concentrated. The residue was chromatographed via ISCO to yield N-(3-(2,6-difluoropyridin-4-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide as a light brown solid (37%). LCMS (m/z) (M+H)=393.0, Rt=1.09 min.

Reference： [1]Patent: US2014/275003,2014,A1 .Location in patent: Paragraph 0523; 0524

8
[ 10244-24-3 ]
[ 876322-58-6 ]
N-(3-(2,6-dimorpholinopyrimidin-4-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; at 120℃; for 0.333333h;Microwave irradiation;	Step 1. To a solution of <strong>[10244-24-3]4,4'-(6-chloropyrimidine-2,4-diyl)dimorpholine</strong> (1.0 equiv.) and Intermediate A (1.1 equiv.) in DME and 2M sodium carbonate (3:1, 0.2 M) was added PdCl2(dppf)-DCM adduct (0.500 equiv.) in a microwave vial equipped with a stir bar. The reaction was heated to 120 C. for 20 min in the microwave. The organic phase was dried with sodium sulfate, filtered and concentrated. The crude material was purified via preparative reverse phase HPLC. Upon lyophilization of the pure fractions, N-(3-(2,6-dimorpholinopyrimidin-4-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide was isolated as the TFA salt in 37% yield. LCMS (m/z) (M+H)=528.3, Rt=0.80 min, 1H NMR (400 MHz, <dmso>) delta ppm 2.21-2.35 (m, 3H) 3.68 (br. s., 8H) 3.71 (d, J=4.30 Hz, 8H) 6.50 (br. s., 1H) 7.34 (d, J=8.22 Hz, 1H) 7.70-7.89 (m, 3H) 7.97 (d, J=7.83 Hz, 1H) 8.26 (d, J=7.83 Hz, 1H) 8.29 (s, 1H) 10.59 (br. s., 1H).

Reference： [1]Patent: US2014/275003,2014,A1 .Location in patent: Paragraph 0273; 0274

9
[ 22177-92-0 ]
[ 876322-58-6 ]
N-(4-methyl-3-(6-morpholinopyrimidin-4-yl)phenyl)-3-(trifluoromethyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate In 1,2-dimethoxyethane at 120℃; for 0.333333h; Microwave irradiation;	1.2 Synthesis of N-(4-methyl-3-(6-morpholinopyrimidin-4-yl)phenyl)-3-trifluoromethyl)benzamide Step 2. To a solution of 4-(6-chloropyrimidin-4-yl)morpholine (1.0 equiv.) and Intermediate A (1.1 equiv.) in DME and 2M sodium carbonate (3:1, 0.2 M) was added PdCl2(dppf)-DCM adduct (0.500 equiv.) in a microwave vial equipped with a stir bar. The reaction was heated to 120° C. for 20 min in the microwave. The organic phase was dried with sodium sulfate, filtered and concentrated. The crude material was purified via preparative reverse phase HPLC. Upon lyophilization of the pure fractions, N-(4-methyl-3-(6-morpholinopyrimidin-4-yl)phenyl)-3-(trifluoromethyl)benzamide was isolated as the TFA salt in 52% yield. 1H NMR (400 MHz, ) δ ppm 2.28 (s, 3H) 3.67-4.02 (m, 8H) 7.09 (s, 1H) 7.35 (d, J=8.22 Hz, 1H) 7.65 (s, 2H) 7.78-7.84 (m, 1H) 7.92 (d, J=2.35 Hz, 1H) 8.16 (s, 2H) 8.64 (s, 1H). LCMS (m/z) (M+H)=443.2, Rt=0.77 min. The compounds listed below were prepared using methods similar to those described for the preparation of Example 1 using the appropriate starting materials.
51%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate In 1,4-dioxane; water at 110℃; for 2h; Inert atmosphere;

Reference： [1]Current Patent Assignee: NOVARTIS AG; Barsanti, Paul A.; Burger, Matthew; Lou, Yan; Nishiguchi, Gisele; Polyakov, Valery; Ramurthy, Savithri; Rico, Alice; Setti, Lina; Smith, Aaron; Taft, Benjamin; Tanner, Huw; DiPesa, Alan; Yusuff, Naeem - US2014/275003, 2014, A1 Location in patent: Paragraph 0250; 0252
[2]Nishiguchi, Gisele A.; Rico, Alice; Tanner, Huw; Aversa, Robert J.; Taft, Benjamin R.; Subramanian, Sharadha; Setti, Lina; Burger, Matthew T.; Wan, Lifeng; Tamez, Victoriano; Smith, Aaron; Lou, Yan; Barsanti, Paul A.; Appleton, Brent A.; Mamo, Mulugeta; Tandeske, Laura; Dix, Ina; Tellew, John E.; Huang, Shenlin; Mathews Griner, Lesley A.; Cooke, Vesselina G.; Van Abbema, Anne; Merritt, Hanne; Ma, Sylvia; Gampa, Kalyani; Feng, Fei; Yuan, Jing; Wang, Yingyun; Haling, Jacob R.; Vaziri, Sepideh; Hekmat-Nejad, Mohammad; Jansen, Johanna M.; Polyakov, Valery; Zang, Richard; Sethuraman, Vijay; Amiri, Payman; Singh, Mallika; Lees, Emma; Shao, Wenlin; Stuart, Darrin D.; Dillon, Michael P.; Ramurthy, Savithri [Journal of Medicinal Chemistry, 2017, vol. 60, # 12, p. 4869 - 4881]

10
[ 35944-64-0 ]
[ 876322-58-6 ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

11
[ 709652-82-4 ]
[ 876322-58-6 ]
[ 76-05-1 ]
N-(3-(6-amino-5-cyanopyridin-3-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide tifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%		To a solution of <strong>[709652-82-4]2-amino-5-bromonicotinonitrile</strong> (1.4 equiv.) in toluene and ethanol (2.5:1) was added N-(4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)phenyl)-3-(trifluoromethyl)benzamide (1.0 equiv.), Pd(PPh3)4 (0.1 equiv.) and aqueous potassium carbonate (3M, 3.0 equiv.). The reaction was heated in the microwave at 120 C for 40 min. The organic layer was separated and concentrated to dryness under vacuo. The residue was dissolved in DMSO and purified via reverse phase HPLC. The pure fractions were lyophilized to give N-(3-(6-amino-5-cyanopyridin-3-yl)-4-methylphenyl)-3- (trifluoromethyl)benzamide as the TFA salt in 48% yield. 1H NMR (400 MHz, DMSOd6) G 10.45 (s, 1H), 8.30 (s, 1H), 8.25 (d, J=2.0, 1H), 8.23 (d, J=2.0, 1H), 7.97 (d, J=8.0, 1H), 7.95 (d, J=4.0, 1H), 7.79 (t, J=8.0, 1H), 7.72 (dd, J=8.0, 2.0, 1H), 7.61 (d, J=4.0, 1H), 7.30 (d, J=12.0, 1H), 2.23 (s, 3H). LCMS (m/z) (M+H) = 397.1, Rt = 0.91 min.

Reference： [1]Patent: WO2016/38583,2016,A1 .Location in patent: Paragraph 00157

12
[ 35944-64-0 ]
[ 73183-34-3 ]
[ 876322-58-6 ]

Reference： [1]Patent: EP2269993,2011,A1

Same Skeleton Products

Related Products

Historical Records

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

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

[ CAS No. 876322-58-6 ] {[proInfo.proName]}

Quality Control of [ 876322-58-6 ]

Related Doc. of [ 876322-58-6 ]

Product Details of [ 876322-58-6 ]

Safety of [ 876322-58-6 ]

Application In Synthesis of [ 876322-58-6 ]

[ 876322-58-6 ] Synthesis Path-Downstream 1~12

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry