There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Structure of 207981-46-2
*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
*For Research Use Only !
Change View
Size | Price | VIP Price | US Stock |
Global Stock |
In Stock | ||
{[ item.pr_size ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | Inquiry {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock 1-2 weeks - Inquiry - | Login | - + | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
1-2weeks
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
CAS No. : | 207981-46-2 |
Formula : | C8H3ClF4O |
M.W : | 226.56 |
SMILES Code : | O=C(Cl)C1=CC(C(F)(F)F)=CC=C1F |
MDL No. : | MFCD00061156 |
InChI Key : | OFVKAIZITGCCDN-UHFFFAOYSA-N |
Pubchem ID : | 2734880 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3265 |
Packing Group: | Ⅱ |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | In tetrahydrofuran; for 16h; | EXAMPLE 26. Synthesis of 2-ChJoro-5-f2-Fluoro-5-TrifluoromethyI-Benzoylamino)-Benzoic Acid (Intermediate 18)18[0162] 5-Amino-2-chIoro-benzoic acid (0.4 g, 2.32 mmol) was diluted with THF (12 mL), treated with 2-fluoro-5-trifluoromethyl-benzoyl chloride (0.388 g, 2.56 mmol) and stirred for 16h. Solvents were then removed and resulting solids were triturated with DCM. After filtration, the title compound was obtained as a white solid (0.5 g, 60%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 150℃; for 0.5h;Microwave irradiation; | Example 2811-({5-[2-Fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}methyl)-2- propyl-4-(trifluoromethyl)-1 H-indole-5-carbonitrile; To a solution of 2-[5-cyano-2-propyl-4-(trifluoromethyl)-1 /-/-indol-1-yl]-Λ/- hydroxyethanimidamide (Example 275A) (0.100 g, 0.308 mmol) in anhydrous acetonitrile (3.0 ml_) under N2, was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.279 g, 1.23 mmol) and N,N-diisopropylethylamine (0.50 ml_, 5.21 mmol). The mixture was then heated in a microwave at 15O0C for 30 min. Upon cooling, the mixture was poured onto a biotage prepak column and the mixture was purified by flash chromatography (0-25% EtOAc-hexanes gradient) to give 0.069 g (45% yield) of pure product: MS (ES) m/z 496 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 73 N-{4-amino-2-methyl-3-[4-([(3-methylphenyl)amino]carbonyl}amino)phenyl]thieno[3,2-c]pyridin-7-yl}-2-fluoro-5-(trifluoromethyl)benzamide The desired product was prepared by substituting 2-fluoro-5-trifluromethylbenzoyl chloride for nicotinoyl chloride in Examples 72C-D. 1H NMR (300 MHz, DMSO-d6) δ 2.29 (s, 6H), 5.36 (s, 2H), 6.81 (d, J=7.12 Hz, 1H), 7.17 (t, J=7.80 Hz, 1H), 7.27 (d, J=12.88 Hz, 2H), 7.32 (s, 2H), 7.64 (d, J=8.81 Hz, 3H), 7.83 (s, 1H), 8.04 (d, J=5.76 Hz, 1H), 8.09 (s, 1H), 8.69 (s, 1H), 8.91 (s, 1H), 10.46 (s, 1H); MS (ESI(+)) m/e 594 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1-methyl-pyrrolidin-2-one; at 20℃; for 24h; | Example 154; C-Fluoro-N-([3-(3-methanesulfonylmethyl-phenylamino)-phenyl]-methyl-amino}- methyl-1H-benzoimidazol-2-yl)-trifluoromethyl-benzamide; To a solution of [(2-Chloro-pyrimidin-4-yl)-methyl-amino]-methyl-H-benzoimidazol- 2-yl}-carbamic acid tert-butyl ester (2.86g, 7.4 mmol) and 3- [(methylsulfonyl) methyl] aniline (1.5 g, 8. 1mmol) in isopropanol (70 ml) was added a solution of HCI (1 drop, 4 M in dioxane) and the reaction was heated to 70C. After 16 hours, the reaction mixture was concentrated in vacuo and neutralized with the addition of saturated NaHC03 solution. The mixture was filtered to give N5- [3- (3- Methanesulfonylmethyl-phenylamino)-phenyl]-1, N5-dimethyl-1 H-benzoimidazole- 2,5-diamine as an off white solid, which was used to produce the titled compound. To the solution of N5- [3- (3-Methanesulfonylmethyl-phenylamino)-phenyl]-1, N5-dimethyl-1 H-benzoimidazole-2, 5-diamine (36 mg, 0.083 mmol) in NMP was added fluoro-trifluoromethyl-benzoyl chloride (38µl, 0.25 mmol). The reaction mixture was stirred at rt for 24 hrs and then purified with Gilson HPLC to give C-Fluoro-N- ( { [3- (3- methanesulfonylmethyl-phenylamino)-phenyl]-methyl-amino}-methyl-1 H- benzoimidazol-2-yl)-trifluoromethyl-benzamide (20mg, 38%). MS (ESI) m/z = 628 [M+H] +, LC/MS Rt (min) 2.03 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Potassium ethyl malonate (10.2 g, 60 mmol), MgCl2(6.3 g, 66 mmol), and triethylamnine (28 ml, 200 mmol) were suspended in ethyl acetate (200 ml) and heated to 40 C. for 15 hr. A solution of 2-fluoro-5-trifluoromethylbenzoyl chloride (10 g, 44.1 mmol) in ethyl acetate (40 ml) was dropped in slowly (in about one hour). After another hour, the mixture was treated with 2N HCl (200 ml). The organic layer was washed with 0.5 N HCl 2×, 5% K2CO3 2×, brine 2×, and dried over Na2SO4. Evaporation of the solvent and vacuum drying afforded ethyl 3-[2-fluoro-5-(trifluoromethyl)phenyl]-3-oxopropanoate as a pale yellow oil. NMR (500 MHz, CDCl3) δ: 1.25 (t, J=7.4 Hz, 3H); 1.32*; 4.00 (d, JF-H=3 Hz, 2H); 4.21 (q, J=7.4 Hz, 2H); 5.8*; 7.22*; 7.29 (t, J=10.3 Hz, 1H); 7.66*; 7.82 (br, 1H); 8.14*; 8.24 (d, J=6.4 Hz, 1H). Enol form* exists in about 35%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With dmap; In dichloromethane; at 0 - 20℃; | To the solution of 15 (0.1 mmol) and DMAP (0.1 mmol) in CH2Cl2 (1.0 mL), benzoyl chloride (0.3 mmol) was added slowly at 0 C. The reaction mixture was raised to room temperature and stirred overnight. After removal of the solvent, the residue was purified by plate chromatography (eluent: EtOAc/Petrpleum ether=1:3) to give pure compound 20. 95% yield. 1H NMR: δ 12.25 (s, 1H), 9.38 (d, J=3.0 Hz, 1H), 8.98 (d, J=9.5 Hz, 1H), 8.45-8.3 (m, 1H), 8.24 (dd, J=9.5, 3.0 Hz, 1H), 7.9-7.75 (m, 1H), 7.60 (s, 1H), 7.34 (t, J=9.5 Hz, 1H), 3.92 (s, 3H), 1.34 (s, 9H). 13C NMR: δ 162.947, 161.162, 160.907, 147.737, 143.262, 141.331, 134.931, 130.954 (m), 129.722 (m), 128.034 (q), 124.293, 124.142, 121.591, 121.464, 117.626, 117.426, 103.898, 103.625, 69.525, 39.347, 31.065, 28.551. LC-MS: (6.85 min, m/z, ES+): calcd: 488.15; Found: 489.06. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | In toluene; | Step 1. Preparation of Ethyl 2,6-bis(trifluoromethyl)-4-oxo-4H-1-benzopyran-3-carboxylate To a stirred solution of ethyl 4,4,4-trifluoroacetoacetate (3.22 mL, 4.06 g, 22.07 mmol) in toluene (100 mL) was added portion-wise sodium hydride (0.971 g, of 60% oil dispersion reagent, 22.07 mmol) causing gas evolution. After gas evolution has subsided, <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (5.00 g, 22.07 mmol) was added. The reaction was stirred at room temperature for 24 hours, then heated to 105 C. for 24 hours. After cooling to room temperature, the reaction was diluted with diethyl ether and the resulting solution was washed with H2O and brine, dried over MgSO4, filtered and concentrated in vacuo yielding a slightly sticky white solid. This solid was triturated with hexanes yielding the desired ester(3.05 g, 39%) as a white powder: mp 116-120.1 C. 1H NMR(CDCl3/300 MHz) 8.52 (d, 2H, J=1.6 Hz), 8.03 (dd, 1H, J=8.9, 2.2Hz), 7.71 (d, 1H, J=8.9 Hz), 4.48 (q, 2H, J=7.3 Hz), 1.39 (t, 3H, J=7.3 Hz). FABLRMS m/z 355 (M+H). Anal. Calc'd for C14H8F6O4: C, 47.45; H, 2.28. Found: C, 47.59; H, 2.43. |
39% | In toluene; | EXAMPLE 82 STR104 Step 1. Preparation of Ethyl 2,6-bis(trifluoromethyl)-4-oxo-4H-1-benzopyran-3-carboxylate. To a stirred solution of ethyl 4,4,4-trifluoroacetoacetate (3.22 mL, 4.06 g, 22.07 mmol) in toluene (100 mL) was added portion-wise sodium hydride (0.971 g, of 60% oil dispersion reagent, 22.07 mmol) causing gas evolution. After gas evolution has subsided, <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (5.00 g, 22.07 mmol) was added. The reaction was stirred at room temperature for 24 hours, then heated to 105 C. for 24 hours. After cooling to room temperature, the reaction was diluted with diethyl ether and the resulting solution was washed with H2 O and brine, dried over MgSO4, filtered and concentrated in vacuo yielding a slightly sticky white solid. This solid was triturated with hexanes yielding the desired ester(3.05 g, 39%) as a white powder: mp 116-120.1 C. 1 H NMR (CDCl3 /300 MHz) 8.52 (d, 2H, J=1.6 Hz), 8.03 (dd, 1H, J=8.9, 2.2Hz), 7.71 (d, 1H, J=8.9 Hz), 4.48 (q, 2H, J=7.3 Hz), 1.39 (t, 3H, J=7.3 Hz). FABLRMS m/z 355 (M+H). Anal. Calc'd for C14 H8 F6 O4: C, 47.45; H, 2.28. Found: C, 47.59; H, 2.43. |
39% | In toluene; | Step 1. Preparation of Ethyl 2,6-bis(trifluoromethyl)-4-oxo-4H-1-benzopyran-3-carboxylate. To a stirred solution of ethyl 4,4,4-trifluoroacetoacetate (3.22 mL, 4.06 g, 22.07 mmol) in toluene (100 mL) was added portion-wise sodium hydride (0.971 g, of 60% oil dispersion reagent, 22.07 mmol) causing gas evolution. After gas evolution has subsided, <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (5.00 g, 22.07 mmol) was added. The reaction was stirred at room temperature for 24 hours, then heated to 105 C. for 24 hours. After cooling to room temperature, the reaction was diluted with diethyl ether and the resulting solution was washed with H2 O and brine, dried over MgSO4, filtered and concentrated in vacuo yielding a slightly sticky white solid. This solid was triturated with hexanes yielding the desired ester(3.05 g, 39%) as a white powder: mp 116-120.1 C. 1 H NMR (CDCl3 /300 MHz) 8.52 (d, 2H, J=1.6 Hz), 8.03 (dd, 1H, J=8.9, 2.2 Hz), 7.71 (d, 1H, J=8.9 Hz), 4.48 (q, 2H, J=7.3 Hz), 1.39 (t, 3H, J=7.3 Hz). FABLRMS m/z 355 (M+H). Anal. Calc'd for C14 H8 F6 O4: C, 47.45; H, 2.28. Found: C, 47.59; H, 2.43. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; at 20℃; for 12h; | To a solution of 6-(5-amino-2-methylphenyl)quinazolin-2-amine (500 mg, 1.97 mmol) in THF (15 ml) at room temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.297 ml, 1.97 mmol). A white precipitate forms. The reaction is stirred at room temperature for 12 hours, at which point the solvent is removed under reduced pressure. The mixture was partitioned between ethyl acetate and aqueous saturated sodium bicarbonate. The organics were washed with brine and dried with magnesium sulfate. Filtration and concentration afforded the title compound. MS (m/z)=445 (M+H+); calc'd for C21H13F5N4O: 444.37 Alternatively, the crude product, as an HCl salt, may be carried forward without a basic workup. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With triethylamine; In dichloromethane; at 20℃; | Example 1G (E)-N-(5-tert-butyl-2-(cyclopropylmethyl)-1-methyl-1H-pyrazol-3(2H)-ylidene)-2-fluoro-5-(trifluoromethyl)benzamide To Example 1F (3.52 g, 17 mmol) in CH2Cl2 (50 mL) was added triethylamine (7.1 mL, 51 mmol), followed by addition of <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (3.85 g, 17 mmol) dropwise. The mixture was stirred at ambient temperature for 2 hours. Water (20 mL) and CH2Cl2 (20 mL) were added. The organic layer was separated, washed with brine, and concentrated. The residue was purified by column chromatography using an Analogix Intelliflash280 (SiO2, eluted with a gradient of 15-100% hexanes in solvent B, solvent B: 10:1:0.5 ethyl acetate:methanol:triethylamine) to afford the title compound (6.3 g, 93%). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.42-0.56 (m, 4H), 1.15-1.29 (m, 1H), 1.40 (s, 9H), 3.95 (s, 3H), 4.24 (d, J=7.14 Hz, 2H), 6.84 (s, 1H), 7.33-7.43 (m, 1H), 7.70-7.78 (m, 1H), 8.12 (dd, J=6.74, 2.38 Hz, 1H); MS (DCI) m/z 398 [M+H]+. |
93% | With sodium hydroxide; In tetrahydrofuran; water; at 0 - 20℃; | Example 9G; (E)-N-(5-tert-butyl-2-(cyclopropylmethyl)-1-methyl-1H-pyrazol-3(2H)-ylidene)-2-fluoro-5-(trifluoromethyl)benzamide; To Example 9F (3.52 g, 17 mmol) in THF (20 mL) was added sodium hydroxide (2.72 g, 68 mmol) in water (5.00 mL) following by addition of 2-bromo-5-(trifluoromethyl)benzoyl chloride (3.85 g, 17 mmol) in THF (5 mL) dropwise at 0 C. The mixture was stirred at room temperature for 1 hour then water (20 mL) and ethyl acetate (30 mL) were added. The organic extract was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of the residue by flash chromatography (silica gel; eluted with a gradient of 10-50% hexanes in solvent B, solvent B: 10:1:0.5 ethyl acetate:methanol:triethylamine) afforded 6.3 g (93%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.42-0.56 (m, 4H), 1.15-1.29 (m, 1H), 1.42 (m, 9H), 3.95 (s, 3H), 4.24 (d, J=7.14 Hz, 2H), 6.84 (s, 1H), 7.33-7.43 (m, 1H), 7.70-7.78 (m, 1H), 8.12 (dd, J=6.74, 2.38 Hz, 1H); MS (+DCI) m/z 398 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With triethylamine; In tetrahydrofuran; at 50℃; for 4h; | Example 36A (R,Z)-N-(5-tert-butyl-3-((tetrahydrofuran-2-yl)methyl)thiazol-2(3H)-ylidene)-2-fluoro-5-(trifluoromethyl)benzamide To a solution of the product of Example 17B (0.62 g, 2.6 mmol) in THF (15 mL) was added triethylamine (1.1 mL, 7.7 mmol) followed by <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.39 mL, 2.6 mmol) in 5 mL THF via cannula. This mixture was warmed to 50 C. and was allowed to stir for 4 h. The mixture was quenched with saturated, aqueous NH4Cl (5 mL) and diluted with EtOAc (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3*5 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (SiO2, 60% hexanes in EtOAc) to give the title compound (0.44 g, 1.0 mmol, 40% yield). MS (DCI/NH3) m/z 431 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine; In tetrahydrofuran; at 20℃; for 1h; | Example 146; N-r(5Z)-2-tert-butyl-4-isobutylisothiazol-5(2H)-ylidene]-2-ethoxy-5- (trifluoromethyl)benzamide; Example 146 A; ethyl 2-fluoro-5-(trifluoromethyl)benzoate; To a solution of <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (5.0 g, 22.0 mmol) in THF (25 mL) was added Et3N (3.1 mL, 22.0 mmol) followed by EtOH (1.3 mL, 22.0 mmol). This mixture was stirred at ambient temperature for 1 h and quenched with saturated, aqueous NH4Cl (10 mL). The layers were separated and the aqueous layer was extracted with 3 X 10 mL EtOAc and the combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (SiO2, 60% hexanes in EtOAc) to give the title compound (4.8 g, 20.3 mmol, 92% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.42 (t, J=7.1 Hz, 3 H), 4.43 (q, J=7.1 Hz, 2 H), 7.23 - 7.34 (m, 1 H), 7.74 - 7.82 (m, 1 H), 8.23 (dd, J=6.3, 2.4 Hz, 1 H). |
92% | With triethylamine; In tetrahydrofuran; at 20℃; for 1h; | Example 146 A; ethyl 2-fluoro-5 -(trifluoromethyl)benzoate; To a solution of <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (5.0 g, 22.0 mmol) in THF (25 mL) was added Et3N (3.1 mL, 22.0 mmol) followed by EtOH (1.3 mL, 22.0 mmol). This mixture was stirred at ambient temperature for 1 h and quenched with saturated, aqueous NH4Cl (10 mL). The layers were separated and the aqueous layer was extracted with 3 X 10 mL EtOAc and the combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (SiO2, 60% hexanes in EtOAc) to give the title compound (4.8 g, 20.3 mmol, 92% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.42 (t, J=I λ Hz, 3 H), 4.43 (q, J=7.1 Hz, 2 H), 7.23 - 7.34 (m, 1 H), 7.74 - 7.82 (m, 1 H), 8.23 (dd, J=6.3, 2.4 Hz, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 38H N-(3-tert-butyl-1-(((2R,3R)-3-fluorotetrahydrofuran-2-yl)methyl)-1H-pyrazol-5-yl)-2-fluoro-5-(trifluoromethyl)benzamide The title compound was prepared using the procedure as described in Example 32B substituting Example 38G for Example 32A and <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> for 2-methoxy-5-(trifluoromethyl)benzoyl chloride. MS (DCI/NH3) m/z 432 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 0 - 20℃; | To a solution of 5-tert-butyl-1,3,4-thiadiazol-2-amine (1.57 g, 10 mmol) and <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (2.27 g, 10 mmol) in CH2Cl2 (45 mL) at 0 C. was added dropwise triethylamine (1.7 mL, 12 mmol) and the reaction was allowed to warm to ambient temperature and stirred for 12 hours. The mixture was then washed with water, brine, dried with MgSO4, filtered, and concentrated under reduced pressure to afford 3.2 g of the title compound. MS (DCI/NH3) m/z 348 (M+H) | |
With triethylamine; In dichloromethane; at 20℃; | Example 3A N-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide To a solution of 5-tert-butyl-1,3,4-thiadiazol-2-amine (1.57 g, 10 mmol) and <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (2.27 g, 10 mmol) in CH2Cl2 (45 mL) at 0 C. was added triethylamine (1.7 mL, 12 mmol) dropwise and the reaction mixture was allowed to warm to ambient temperature for 12 hours. The mixture was then washed with water, brine, dried with MgSO4, filtered, and concentrated under reduced pressure to afford 3.2 g of the title compound. MS (DCI/NH3) m/z 348 (M+H)+. | |
With triethylamine; In dichloromethane; at 0 - 20℃; | Example 45A N-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide To a solution of 5-tert-butyl-1,3,4-thiadiazol-2-amine (1.57 g, 10 mmol) and <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (2.27 g, 10 mmol) in CH2Cl2 (45 mL) at 0 C. was added dropwise triethylamine (1.7 mL, 12 mmol) and the reaction mixture was allowed to warm to ambient temperature for 12 h. The mixture was then washed with water, brine, dried with MgSO4, and concentrated under reduced pressure to afford 3.2 g of the title compound. MS (DCI/NH3) m/z 348 (M+H)+. |
With triethylamine; In dichloromethane; at 0 - 20℃; | To a solution of 5-tert-butyl-1,3,4-thiadiazol-2-amine (1.57 g, 10 mmol) and <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (2.27 g, 10 mmol) in CH2Cl2 (45 mL) at 0 C. was added dropwise triethylamine (1.7 mL, 12 mmol) and the reaction was allowed to warm to ambient temperature and stirred for 12 hours. The mixture was then washed with water, brine, dried with MgSO4, filtered, and concentrated under reduced pressure to afford 3.2 g of the title compound. MS (DCI/NH3) m/z 348 (M+H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With triethylamine; In tetrahydrofuran; at 20 - 50℃; | Example 42B (Z)-tert-butyl 3-((5-tert-butyl-2-(2-fluoro-5-(trifluoromethyl)benzoylimino)thiazol-3(2H)-yl)methyl)azetidine-1-carboxylate To a solution of the product of Example 42A (4.1 g, 12.5 mmol) in tetrahydrofuran (40 mL) was added triethylamine (5.2 mL, 37.6 mmol) followed by <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (2.0 mL, 13.2 mmol). This mixture was warmed to 50 C. and was allowed to stir for 90 min then the mixture was cooled to ambient temperature and was stirred for 16 h. The mixture was quenched with saturated, aqueous NH4Cl (20 mL) and diluted with ethyl acetate (20 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3*10 mL). The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (SiO2, 60% hexanes in ethyl acetate) to give the title compound (5.2 g, 10.0 mmol, 80% yield). MS (DCI/NH3) m/z 516 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.0% | With triethylamine; In tetrahydrofuran; at 10 - 30℃; for 1h; | To a solution of tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (1.00 g, 4.62 mmol) and triethylamine (0.967 ml, 6.94 mmol) in tetrahydrofuran (20 ml) was added 5-trifluoromethyl-2-fluorobenzoyl chloride (0.837 ml, 5.54 mmol) at room temperature, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give the object product (1.26 g, 67.0%) as an oil. 1H-NMR (CDCl3) δ; 1.47 (9H, s), 3.02 (3H, br s), 3.29 (1H, br s), 3.61 (1H, br s), 3.79 (1H, br s), 4.08-4.22 (2H, br s), 4.51-4.54 (1H, m), 4.85 (1H, br s), 7.21-7.26 (1H, m), 7.68-7.72 (2H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 10D N-{3-tert-butyl-1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-5-yl}-2-fluoro-5-(trifluoromethyl)benzamide To a solution of the product of Example 10C (7.8 g, 35.0 mmol) and triethylamine (14.6 mL, 105 mmol) in THF (60 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (5.3 mL, 35.0 mmol) dropwise over 10 min. The mixture was stirred at ambient temperature for 3 h. The mixture was quenched with saturated, aqueous NaHCO3(20 mL) and diluted with EtOAc (20 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3*10 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 40% hexanes/EtOAc) gave the title compound (11.0 g, 26.6 mmol, 76% yield). MS (DCI/NH3) m/z 414 (M+H)+. | ||
660 mg | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 4h;Inert atmosphere; | To a solution of 2-fluoro-5-trifluoromethylbenzoic acid (500 mg, 2.4 mmol) in anhydrous dichloromethane (10 mL) was added oxalyl chloride (410 μL, 4.8 mmol) followed by N,N-dimethylformamide (2 drops) and the mixture was stirred at room temperature for 3 hours. The volatiles were removed under a stream of nitrogen and the residue taken up in dichloromethane and added slowly to a solution of 11 (540 mg, 2.4 mmol) and N,N-diisopropylethylamine (1.0 mL, 6.0 mmol) in dichloromethane (10 mL) at 0 C. The mixture was warmed to room temperature and stirred for 4 hours. The mixture was diluted with dichloromethane (30 mL) and washed with saturated aqueous sodium hydrogen carbonate (20 mL) and saturated aqueous ammonium chloride. The organic phase was dried over anhydrous magnesium sulfate, concentrated under reduced pressure and purified by flash column chromatography using ethyl acetate, hexane (0:1 to 3:7) as an eluent to obtain the title compound (660 mg, 67%) as an off-white waxy solid, Rf: 0.45 (2:3 ethyl acetate, hexane); IR (vmax (neat)): 3294, 2962, 1680, 1547, 1326, 1232, 1129, 1092 cm-1; 1H NMR (400 MHz, CDCl3): δ 1.31 (9H, s), 1.62-1.76 (2H, m), 1.80-1.94 (1H, m), 2.00-2.08 (1H, m), 3.68-3.89 (2H, m), 4.11 (1H, dd, J = 15.1, 5.8 Hz), 4.18-4.29 (1H, m), 4.41 (1H, dd, J = 15.4, 1.9 Hz), 6.55 (1H, s), 7.28-7.36 (1H, m), 7.74-7.84 (1H, m), 8.39 (1H, dd, J = 6.9, 2.5 Hz), 10.08 (1H, d, J = 8.1 Hz) ppm; 13C NMR (100 MHz, CDCl3): δ 25.9, 28.1, 30.6, 32.4, 53.0, 68.8, 79.7, 95.6, 117.3 (d, J = 25.3 Hz), 122.4 (d, J = 13.8 Hz), 122.9 (q, J = 272.1 Hz), 128.0 (q, J = 30.3 Hz), 130.1-130.2 (m), 130.7-140.0 (m), 136.4, 159.0 (d, J = 2.8 Hz), 161.0, 161.9 (d, J = 255.2 Hz) ppm; 19F NMR (282 MHz, DMSO-d6): δ -62.3 (CF3), -108.4 (CF) ppm; LRMS (+ESI) m/z: 436.2 ([M+Na]+ 100%), 849.2 ([2M+Na]+ 43%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With pyridine; In tetrahydrofuran; at 60℃; for 16h; | To a solution of Example 30A (0.7 g, 2.6 mmol) in tetrahydrofuran (20 mL) were added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.46 mL, 3.1 mmol, Aldrich) and pyridine (0.62 mL, 7.6 mmol). After stirring at 60 C. for 16 h, the reaction mixture was cooled and quenched with saturated NaHCO3 (20 mL). The aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix Intelliflash280 (SiO2, O-25% ethyl acetate in methylene chloride) to afford 0.75 g (67%) of the title compound. MS (ESI+) m/z 438 (M+H)+ |
67% | With pyridine; In tetrahydrofuran; at 60℃; for 16h; | To a solution of Example 30A (0.7 g, 2.6 mmol) in tetrahydrofuran (20 mL) were added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.46 mL, 3.1 mmol, Aldrich) and pyridine (0.62 mL, 7.6 mmol). After stirring at 60 C. for 16 h, the reaction mixture was cooled and quenched with saturated NaHCO3 (20 mL). The aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix Intelliflash280 (SiO2, O-25% ethyl acetate in methylene chloride) to afford 0.75 g (67%) of the title compound. MS (ESI+) m/z 438 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With triethylamine; In tetrahydrofuran; at 20℃; for 1.5h; | To a solution of Example 81A (30.3 g, 155 mmol) and Et3N (64.9 mL, 465 mmol) in THF (500 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (23.5 mL, 155 mmol) dropwise over 30 minutes via syringe pump. The mixture was stirred at ambient temperature for 1 hour then diluted with saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (200 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification of the residue by column chromatography (SiO2, 50% hexanes/EtOAc) provided the title compound (50.3 g, 130 mmol, 84% yield). MS (ESI+) m/z 386 (M+H)+ |
84% | With triethylamine; In tetrahydrofuran; at 20℃; | Example 4B N-(1-butyl-3-tert-butyl-1H-pyrazol-5-yl)-2-fluoro-5-(trifluoromethyl)benzamide To a solution of Example 4A (30.3 g, 155 mmol) and Et3N (64.9 mL, 465 mmol) in THF (500 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (23.5 mL, 155 mmol) dropwise over 30 minutes via syringe pump. The mixture was stirred at ambient temperature for 1 hour then diluted with saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (200 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3*20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification of the residue by column chromatography (SiO2, 50% hexanes/EtOAc) provided the title compound (50.3 g, 130 mmol, 84% yield). MS (ESI+) m/z 386 (M+H)+. |
84% | With triethylamine; In tetrahydrofuran; at 20℃; for 1.5h; | To a solution of Example 81A (30.3 g, 155 mmol) and Et3N (64.9 mL, 465 mmol) in THF (500 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (23.5 mL, 155 mmol) dropwise over 30 minutes via syringe pump. The mixture was stirred at ambient temperature for 1 hour then diluted with saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (200 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification of the residue by column chromatography (SiO2, 50% hexanes/EtOAc) provided the title compound (50.3 g, 130 mmol, 84% yield). MS (ESI+) m/z 386 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With triethylamine; In tetrahydrofuran; at 20℃; for 2.01667h; | To a solution of Example 87B (7.01 g, 29.8 mmol) and Et3N (12.5 mL, 89 mmol) in THF (30 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (4.5 mL, 29.8 mmol) dropwise over 1 min. The mixture was stirred at ambient temperature for 2 hours then was partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×5 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography (SiO2, 70% hexanes/EtOAc) provided the title compound (6.2 g, 14.5 mmol, 49% yield). MS (DCI/NH3) m/z 426 (M+H)+ |
49% | With triethylamine; In tetrahydrofuran; at 20℃; for 2.01667h; | To a solution of Example 87B (7.01 g, 29.8 mmol) and Et3N (12.5 mL, 89 mmol) in THF (30 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (4.5 mL, 29.8 mmol) dropwise over 1 min. The mixture was stirred at ambient temperature for 2 hours then was partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×5 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography (SiO2, 70% hexanes/EtOAc) provided the title compound (6.2 g, 14.5 mmol, 49% yield). MS (DCI/NH3) m/z 426 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With triethylamine; In tetrahydrofuran; at 20℃; for 3h; | To a solution of Example 135B (2.0 g, 8.1 mmol) and Et3N (3.4 mL, 24.3 mmol) in THF (40 mL) was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (1.2 mL, 8.1 mmol). The mixture was allowed to stir at ambient temperature for 3 h then partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted EtOAc (3×10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes/EtOAc then 100% EtOAc then 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (2.9 g, 6.5 mmol, 80% yield). MS (ESI+) m/z 440 (M+H)+ |
80% | With triethylamine; In tetrahydrofuran; at 20℃; for 3h; | To a solution of Example 135B (2.0 g, 8.1 mmol) and Et3N (3.4 mL, 24.3 mmol) in THF (40 mL) was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (1.2 mL, 8.1 mmol). The mixture was allowed to stir at ambient temperature for 3 h then partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted EtOAc (3×10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes/EtOAc then 100% EtOAc then 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (2.9 g, 6.5 mmol, 80% yield). MS (ESI+) m/z 440 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With triethylamine; In dichloromethane; at 20℃;Product distribution / selectivity; | Example 1AN-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydro furan-2-ylmethyl]-1,3-thiazol-2(3H)-ylidene]-2-fluoro-5-(trifluoromethyl)benzamideTo Example 22A (3.0 g, 8.15 mmol) and triethylamine (3.41 mL, 24.44 mmol) in CH2Cl2 (30 mL) was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (1.481 mL, 9.78 mmol) dropwise. The mixture was stirred at room temperature for 2 h. Water and CH2Cl2 (100 mL/100 mL) were added and the organic layer was washed with brine and concentrated. Purification by flash chromatography (silica gel, EtOAc/hexane in 10-50% gradient) afforded 2.9 g (83%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.33 (s, 9H), 1.60-2.01 (m, 4H), 3.60-3.71 (m, 1H), 3.74-3.87 (m, 1H), 4.18-4.40 (m, 3H), 7.35 (s, 1H), 7.47-7.59 (m, 1H), 7.88-7.97 (m, 1H), 8.31 (dd, J=6.74, 2.78 Hz, 1H); MS (ESI) m/z 431 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 4h; | General procedure: To a suspension of the carboxylic acid (5.00 mmol) in CH2Cl2 (15 mL) was added DMF (2 drops) followed by oxalylchloride (0.530 mL, 6.25 mmol). The reaction mixture was stirred at rt for 4 h, and then evaporated to dryness. Theacid chloride thus prepared was dissolved in CH2Cl2 (15 mL) at 0 C. Triethylamine (2.10 mL, 15.0 mmol) and added,followed by either ethylamine hydrochloride, benzylamine, or 2,4-dimethoxybenzylamine (7.50 mmol). The reactionmixture was allowed to warm to rt and stirred for a further 15 h. Water (50 mL) was added, and the aqueous phaseextracted with CH2Cl2 (3 × 50 mL). The combined organics were washed with saturated Na2CO3 (20 mL), dried overMgSO4, subjected to filtration, and concentrated in vacuo. The crude product was purified by flash chromatographyon silica gel, eluting with EtOAc/hexanes/CH2Cl2, to afford the title compound. | |
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 3h;Inert atmosphere; | To a solution of 2-fluoro-5-trifluoromethylbenzoic acid (500 mg, 2.4 mmol) in anhydrous dichloromethane (10 mL) was added oxalyl chloride (410 μL, 4.8 mmol) followed by N,N-dimethylformamide (2 drops) and the mixture was stirred at room temperature for 3 hours. The volatiles were removed under a stream of nitrogen and the residue taken up in dichloromethane and added slowly to a solution of 11 (540 mg, 2.4 mmol) and N,N-diisopropylethylamine (1.0 mL, 6.0 mmol) in dichloromethane (10 mL) at 0 C. The mixture was warmed to room temperature and stirred for 4 hours. The mixture was diluted with dichloromethane (30 mL) and washed with saturated aqueous sodium hydrogen carbonate (20 mL) and saturated aqueous ammonium chloride. The organic phase was dried over anhydrous magnesium sulfate, concentrated under reduced pressure and purified by flash column chromatography using ethyl acetate, hexane (0:1 to 3:7) as an eluent to obtain the title compound (660 mg, 67%) as an off-white waxy solid, Rf: 0.45 (2:3 ethyl acetate, hexane); IR (vmax (neat)): 3294, 2962, 1680, 1547, 1326, 1232, 1129, 1092 cm-1; 1H NMR (400 MHz, CDCl3): δ 1.31 (9H, s), 1.62-1.76 (2H, m), 1.80-1.94 (1H, m), 2.00-2.08 (1H, m), 3.68-3.89 (2H, m), 4.11 (1H, dd, J = 15.1, 5.8 Hz), 4.18-4.29 (1H, m), 4.41 (1H, dd, J = 15.4, 1.9 Hz), 6.55 (1H, s), 7.28-7.36 (1H, m), 7.74-7.84 (1H, m), 8.39 (1H, dd, J = 6.9, 2.5 Hz), 10.08 (1H, d, J = 8.1 Hz) ppm; 13C NMR (100 MHz, CDCl3): δ 25.9, 28.1, 30.6, 32.4, 53.0, 68.8, 79.7, 95.6, 117.3 (d, J = 25.3 Hz), 122.4 (d, J = 13.8 Hz), 122.9 (q, J = 272.1 Hz), 128.0 (q, J = 30.3 Hz), 130.1-130.2 (m), 130.7-140.0 (m), 136.4, 159.0 (d, J = 2.8 Hz), 161.0, 161.9 (d, J = 255.2 Hz) ppm; 19F NMR (282 MHz, DMSO-d6): δ -62.3 (CF3), -108.4 (CF) ppm; LRMS (+ESI) m/z: 436.2 ([M+Na]+ 100%), 849.2 ([2M+Na]+ 43%). | |
With thionyl chloride; at 80℃; for 16h;Inert atmosphere; | 2-Fluoro-5-(trifluoromethyl)benzoic acid 7a (382 mg, 1.83 mmol, Shanghai Bide Pharmatech Ltd.) was added to thionyl chloride (5 mL), and the reaction solution was reacted at 80C for 16 hours. The reaction solution was concentrated to obtain the crude title compound 7b (400 mg), which was used directly in the next step without purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With triethylamine; In dichloromethane; at 20℃; | To Example 27F (3.52 g, 17 mmol) in CH2Cl2 (50 mL) was added triethylamine (7.1 mL, 51 mmol), then <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (3.85 g, 17 mmol) dropwise and the mixture was stirred at ambient temperature for 2 hours. Water (20 mL) and CH2Cl2 (20 mL) were added, and the organic layer was washed with brine and concentrated. Purification by flash chromatography (silica gel, MeOH/Et3N (10:1) in EtOAc in 5-40% gradient) afforded 6.3 g (93% yield) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.42-0.56 (m, 4H), 1.15-1.29 (m, 1H), 1.36-1.45 (m, 9H), 3.95 (s, 3H), 4.24 (d, J=7.14 Hz, 2H), 6.84 (s, 1H), 7.33-7.43 (m, 1H), 7.70-7.78 (m, 1H), 8.12 (dd, J=6.74, 2.38 Hz, 1H); MS (+DCI) m/z 398 [M+H]+ |
93% | With triethylamine; In dichloromethane; at 20℃; | To Example 27F (3.52 g, 17 mmol) in CH2Cl2 (50 mL) was added triethylamine (7.1 mL, 51 mmol), then <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (3.85 g, 17 mmol) dropwise and the mixture was stirred at ambient temperature for 2 hours. Water (20 mL) and CH2Cl2 (20 mL) were added, and the organic layer was washed with brine and concentrated. Purification by flash chromatography (silica gel, MeOH/Et3N (10:1) in EtOAc in 5-40% gradient) afforded 6.3 g (93% yield) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.42-0.56 (m, 4H), 1.15-1.29 (m, 1H), 1.36-1.45 (m, 9H), 3.95 (s, 3H), 4.24 (d, J=7.14 Hz, 2H), 6.84 (s, 1H), 7.33-7.43 (m, 1H), 7.70-7.78 (m, 1H), 8.12 (dd, J=6.74, 2.38 Hz, 1H); MS (+DCI) m/z 398 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In tetrahydrofuran; at 20℃; for 3.16667h; | To a solution of the product of Example 1C (7.8 g) and triethylamine (14.6 mL, 105 mmol) in THF (60 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (5.3 mL, 35.0 mmol) dropwise over 10 min. The mixture was stirred at ambient temperature for 3 h. The mixture was quenched with saturated, aqueous NaHCO3 (20 mL) and diluted with EtOAc (20 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 40% hexanes/EtOAc) gave the title compound (11.0 g, 26.6 mmol). MS (DCI/NH3) m/z 414 (M+H)+ | |
With triethylamine; In tetrahydrofuran; at 20℃; for 3.16667h; | To a solution of the product of Example 1C (7.8 g) and triethylamine (14.6 mL, 105 mmol) in THF (60 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (5.3 mL, 35.0 mmol) dropwise over 10 min. The mixture was stirred at ambient temperature for 3 h. The mixture was quenched with saturated, aqueous NaHCO3 (20 mL) and diluted with EtOAc (20 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 40% hexanes/EtOAc) gave the title compound (11.0 g, 26.6 mmol). MS (DCI/NH3) m/z 414 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; at 80℃; for 12h; | A mixture of Example 32B (2 g, 8.92 mmol), 1H-benzo[d][1,2,3]triazol-1-ol hydrate (1.37 g, 8.92 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (1.71 g, 8.92 mmol), 2-fluoro-5-(trifluoromethyl)benzoic acid (1.86 g, 8.92 mmol), and triethylamine (1.86 mL, 13.37 mmol) in 30 mL of THF was heated at 80 C. for 12 hr. The mixture was cooled to room temperature, diluted with EtOAc, washed with NaHCO3, dried over MgSO4 and concentrated. The residue was purified by flash chromatography on SiO2 (Hexanes:EtOAc, 0 to 50%) to give the title compound. MS (ESI) m/z 415 (M+H)+ | |
With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; at 80℃; for 12h; | A mixture of Example 32B (2 g, 8.92 mmol), 1H-benzo[d][1,2,3]triazol-1-ol hydrate (1.37 g, 8.92 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (1.71 g, 8.92 mmol), 2-fluoro-5-(trifluoromethyl)benzoic acid (1.86 g, 8.92 mmol), and triethylamine (1.86 mL, 13.37 mmol) in 30 mL of THF was heated at 80 C. for 12 hr. The mixture was cooled to room temperature, diluted with EtOAc, washed with NaHCO3, dried over MgSO4 and concentrated. The residue was purified by flash chromatography on SiO2 (Hexanes:EtOAc, 0 to 50%) to give the title compound. MS (ESI) m/z 415 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With triethylamine; In tetrahydrofuran; at 20℃; for 2.01667h; | To a solution of Example 86B (0.82 g, 3.9 mmol) and Et3N (1.6 mL, 11.8 mmol) in THF (10 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.60 mL, 3.9 mmol) dropwise over 1 min. The mixture was stirred at ambient temperature for 2 h then was quenched with saturated aqueous NaHCO3 (10 mL) and diluted with EtOAc (10 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×5 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography (SiO2, 60% hexanes/EtOAc) provided the title compound (1.15 g, 2.9 mmol, 74% yield). MS (DCI/NH3) m/z 398 (M+H)+ |
74% | With triethylamine; In tetrahydrofuran; at 20℃; for 2.01667h; | To a solution of Example 86B (0.82 g, 3.9 mmol) and Et3N (1.6 mL, 11.8 mmol) in THF (10 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.60 mL, 3.9 mmol) dropwise over 1 min. The mixture was stirred at ambient temperature for 2 h then was quenched with saturated aqueous NaHCO3 (10 mL) and diluted with EtOAc (10 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×5 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography (SiO2, 60% hexanes/EtOAc) provided the title compound (1.15 g, 2.9 mmol, 74% yield). MS (DCI/NH3) m/z 398 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With triethylamine; In tetrahydrofuran; at 20℃; for 4h; | To a solution of Example 95E (0.53 g, 2.1 mmol) and Et3N (0.88 mL, 6.3 mmol) in THF (10 mL) was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.320 mL, 2.108 mmol). The mixture was stirred at ambient temperature for 4 h then was quenched with saturated aqueous NaHCO3 (10 mL) and diluted with EtOAc (10 mL). The layers were separated and the aqueous phase was extracted EtOAc (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes in EtOAc) afforded the title compound (0.48 g, 1.1 mmol, 52% yield). MS (DCI/NH3) m/z 442 (M+H)+ |
52% | With triethylamine; In tetrahydrofuran; at 20℃; for 4h; | To a solution of Example 95E (0.53 g, 2.1 mmol) and Et3N (0.88 mL, 6.3 mmol) in THF (10 mL) was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.320 mL, 2.108 mmol). The mixture was stirred at ambient temperature for 4 h then was quenched with saturated aqueous NaHCO3 (10 mL) and diluted with EtOAc (10 mL). The layers were separated and the aqueous phase was extracted EtOAc (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes in EtOAc) afforded the title compound (0.48 g, 1.1 mmol, 52% yield). MS (DCI/NH3) m/z 442 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With triethylamine; In tetrahydrofuran; at 20℃; for 4h; | To a solution of Example 99E (0.53 g, 2.4 mmol) and Et3N (1.0 mL, 7.1 mmol) in THF (10 mL) was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.36 mL, 2.4 mmol). The mixture was stirred at ambient temperature for 4 hours then was partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted EtOAc (3×7 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes in EtOAc) afforded the title compound (0.68 g, 1.6 mmol, 69% yield). MS (DCI/NH3) m/z 414 (M+H)+ |
69% | With triethylamine; In tetrahydrofuran; at 20℃; for 4h; | To a solution of Example 99E (0.53 g, 2.4 mmol) and Et3N (1.0 mL, 7.1 mmol) in THF (10 mL) was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.36 mL, 2.4 mmol). The mixture was stirred at ambient temperature for 4 hours then was partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted EtOAc (3×7 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes in EtOAc) afforded the title compound (0.68 g, 1.6 mmol, 69% yield). MS (DCI/NH3) m/z 414 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Sodium hydrogenocarbonate; In water monomer; ethyl acetate; at 20℃; | To a solution of Example 114D (1.5 g, 7.24 mmol) and NaHCO3 (0.91 g, 10.9 mmol) in ethyl acetate (20 mL) and water (15 mL) was added dropwise a solution of 2-fluoro-(5-trifluoromethyl)benzoyl chloride (1.8 g, 8 mmol) in EtOAc (5 mL) and the mixture was left at room temperature with vigorous stirring. The acetate layer was washed with brine, dried with MgSO4 and concentrated under reduced pressure. The residue was purified by chromatography (Hexane-EtOAc 2:1) to afford 2.5 g of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.08-1.30 (m, 7H), 1.37-1.71 (m, 7H), 2.25-2.38 (m, 1H), 2.71-2.95 (m, 1H), 3.90 (d, J=7.5 Hz, 2H), 6.18 (s, 1H), 7.65 (t, J=8.9 Hz, 1H), 7.93-8.09 (m, 2H), 10.49 (s, 1H). MS (DCI/NH3) m/z 398 (M+H)+ | |
With Sodium hydrogenocarbonate; In water monomer; ethyl acetate; at 20℃; | To a solution of Example 114D (1.5 g, 7.24 mmol) and NaHCO3 (0.91 g, 10.9 mmol) in ethyl acetate (20 mL) and water (15 mL) was added dropwise a solution of 2-fluoro-(5-trifluoromethyl)benzoyl chloride (1.8 g, 8 mmol) in EtOAc (5 mL) and the mixture was left at room temperature with vigorous stirring. The acetate layer was washed with brine, dried with MgSO4 and concentrated under reduced pressure. The residue was purified by chromatography (Hexane-EtOAc 2:1) to afford 2.5 g of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.08-1.30 (m, 7H), 1.37-1.71 (m, 7H), 2.25-2.38 (m, 1H), 2.71-2.95 (m, 1H), 3.90 (d, J=7.5 Hz, 2H), 6.18 (s, 1H), 7.65 (t, J=8.9 Hz, 1H), 7.93-8.09 (m, 2H), 10.49 (s, 1H). MS (DCI/NH3) m/z 398 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With triethylamine; In tetrahydrofuran; at 20℃; for 4h; | To a solution of Example 122E (1.3 g, 5.9 mmol) and Et3N (2.5 mL, 17.7 mmol) in THF (15 mL) was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.89 mL, 5.9 mmol). The mixture was allowed to stir at ambient temperature for 4 hours then partitioned between saturated aqueous NaHCO3 (15 mL) and EtOAc (15 mL). The layers were separated and the aqueous phase was extracted EtOAc (3×10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes in EtOAc to 100% EtOAc to 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (1.3 g, 3.2 mmol, 54% yield). MS (DCI/NH3) m/z 416 (M+H)+ |
54% | With triethylamine; In tetrahydrofuran; at 20℃; for 4h; | To a solution of Example 122E (1.3 g, 5.9 mmol) and Et3N (2.5 mL, 17.7 mmol) in THF (15 mL) was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.89 mL, 5.9 mmol). The mixture was allowed to stir at ambient temperature for 4 hours then partitioned between saturated aqueous NaHCO3 (15 mL) and EtOAc (15 mL). The layers were separated and the aqueous phase was extracted EtOAc (3×10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes in EtOAc to 100% EtOAc to 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (1.3 g, 3.2 mmol, 54% yield). MS (DCI/NH3) m/z 416 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triethylamine; In tetrahydrofuran; for 4h; | Triethylamine (0.32 mL, 2.3 mmol) was added to a solution of Example 123D (0.15 g, 0.77 mmol) and <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.12 mL, 0.77 mmol) in THF (2.0 mL). After 4 hours the reaction mixture was partitioned between EtOAc (15 mL) and saturated NaHCO3 (1 mL). The organic extract was washed with water and brine, dried with MgSO4, filtered and concentrated. The residue was purified by chromatography (hexanes:EtOAc:MeOH:Et3N (4:4:1:0.2) to afford the title compound (0.27 g, 0.70 mmol, 91% yield).LCMS (APCI) m/z 396.3 [M+H]+ |
91% | With triethylamine; In tetrahydrofuran; for 4h; | Triethylamine (0.32 mL, 2.3 mmol) was added to a solution of Example 123D (0.15 g, 0.77 mmol) and <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (0.12 mL, 0.77 mmol) in THF (2.0 mL). After 4 hours the reaction mixture was partitioned between EtOAc (15 mL) and saturated NaHCO3 (1 mL). The organic extract was washed with water and brine, dried with MgSO4, filtered and concentrated. The residue was purified by chromatography (hexanes:EtOAc:MeOH:Et3N (4:4:1:0.2) to afford the title compound (0.27 g, 0.70 mmol, 91% yield).LCMS (APCI) m/z 396.3 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With triethylamine; In tetrahydrofuran; at 20℃; for 2.01667h; | To a solution of Example 127B (8.5 g, 38.4 mmol) and triethylamine (16.1 mL, 115 mmol) in THF (75 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (5.82 mL, 38.4 mmol) dropwise over 1 minute. After 2 hours, the mixture was partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×5 mL). The combined organics were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure. The residue was purified by chromatography (SiO2, 70% hexanes/EtOAc) to afford the title compound (12 g, 29.2 mmol, 76% yield). MS (DCI/NH3) m/z 412.3 (M+H)+ |
76% | With triethylamine; In tetrahydrofuran; at 20℃; for 2.01667h; | To a solution of Example 127B (8.5 g, 38.4 mmol) and triethylamine (16.1 mL, 115 mmol) in THF (75 mL) at ambient temperature was added <strong>[207981-46-2]2-fluoro-5-(trifluoromethyl)benzoyl chloride</strong> (5.82 mL, 38.4 mmol) dropwise over 1 minute. After 2 hours, the mixture was partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×5 mL). The combined organics were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure. The residue was purified by chromatography (SiO2, 70% hexanes/EtOAc) to afford the title compound (12 g, 29.2 mmol, 76% yield). MS (DCI/NH3) m/z 412.3 (M+H)+ |
A993259 [126917-10-0]
2-Fluoro-4-(trifluoromethyl)benzoyl chloride
Similarity: 0.98
A755801 [208173-19-7]
2-Fluoro-3-(trifluoromethyl)benzoyl chloride
Similarity: 0.98
A427852 [1261849-09-5]
4-Fluoro-4'-(trifluoromethyl)biphenyl-3-carbonyl chloride
Similarity: 0.96
A379882 [67515-56-4]
4-Fluoro-3-(trifluoromethyl)benzoyl chloride
Similarity: 0.94
A993259 [126917-10-0]
2-Fluoro-4-(trifluoromethyl)benzoyl chloride
Similarity: 0.98
A755801 [208173-19-7]
2-Fluoro-3-(trifluoromethyl)benzoyl chloride
Similarity: 0.98
A427852 [1261849-09-5]
4-Fluoro-4'-(trifluoromethyl)biphenyl-3-carbonyl chloride
Similarity: 0.96
A379882 [67515-56-4]
4-Fluoro-3-(trifluoromethyl)benzoyl chloride
Similarity: 0.94
A993259 [126917-10-0]
2-Fluoro-4-(trifluoromethyl)benzoyl chloride
Similarity: 0.98
A755801 [208173-19-7]
2-Fluoro-3-(trifluoromethyl)benzoyl chloride
Similarity: 0.98
A427852 [1261849-09-5]
4-Fluoro-4'-(trifluoromethyl)biphenyl-3-carbonyl chloride
Similarity: 0.96
A379882 [67515-56-4]
4-Fluoro-3-(trifluoromethyl)benzoyl chloride
Similarity: 0.94
A993259 [126917-10-0]
2-Fluoro-4-(trifluoromethyl)benzoyl chloride
Similarity: 0.98
A755801 [208173-19-7]
2-Fluoro-3-(trifluoromethyl)benzoyl chloride
Similarity: 0.98
A427852 [1261849-09-5]
4-Fluoro-4'-(trifluoromethyl)biphenyl-3-carbonyl chloride
Similarity: 0.96
A379882 [67515-56-4]
4-Fluoro-3-(trifluoromethyl)benzoyl chloride
Similarity: 0.94
A993259 [126917-10-0]
2-Fluoro-4-(trifluoromethyl)benzoyl chloride
Similarity: 0.98
A755801 [208173-19-7]
2-Fluoro-3-(trifluoromethyl)benzoyl chloride
Similarity: 0.98
A427852 [1261849-09-5]
4-Fluoro-4'-(trifluoromethyl)biphenyl-3-carbonyl chloride
Similarity: 0.96
A379882 [67515-56-4]
4-Fluoro-3-(trifluoromethyl)benzoyl chloride
Similarity: 0.94