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[ CAS No. 177787-26-7 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 177787-26-7
Chemical Structure| 177787-26-7
Chemical Structure| 177787-26-7
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Product Details of [ 177787-26-7 ]

CAS No. :177787-26-7 MDL No. :MFCD00083526
Formula : C7H2ClF3O Boiling Point : -
Linear Structure Formula :- InChI Key :YRUNCQNKZIQTEO-UHFFFAOYSA-N
M.W :194.54 Pubchem ID :2777023
Synonyms :

Calculated chemistry of [ 177787-26-7 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 36.5
TPSA : 17.07 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.55 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.76
Log Po/w (XLOGP3) : 2.73
Log Po/w (WLOGP) : 3.74
Log Po/w (MLOGP) : 3.32
Log Po/w (SILICOS-IT) : 3.62
Consensus Log Po/w : 3.03

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.07
Solubility : 0.166 mg/ml ; 0.000851 mol/l
Class : Soluble
Log S (Ali) : -2.74
Solubility : 0.352 mg/ml ; 0.00181 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.8
Solubility : 0.0306 mg/ml ; 0.000157 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.43

Safety of [ 177787-26-7 ]

Signal Word:Danger Class:8
Precautionary Statements:P280-P305+P351+P338-P310 UN#:3265
Hazard Statements:H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 177787-26-7 ]

* 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 [ 177787-26-7 ]

[ 177787-26-7 ] Synthesis Path-Downstream   1~80

  • 1
  • [ 177787-26-7 ]
  • [ 501701-42-4 ]
  • <i>N</i>-[1-(2,4-dimethoxy-benzyloxycarbamoyl)-2-hydroxy-ethyl]-3,4,5-trifluoro-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In pyridine for 0.166667h;
  • 2
  • [ 32677-01-3 ]
  • [ 177787-26-7 ]
  • di-tert-butyl 3,4,5-trifluorobenzoyl-L-glutamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With triethylamine In dichloromethane
  • 3
  • [ 1907-33-1 ]
  • [ 177787-26-7 ]
  • [ 863562-09-8 ]
YieldReaction ConditionsOperation in experiment
78% In tetrahydrofuran at 0 - 20℃; for 2h;
  • 4
  • [ 1018975-59-1 ]
  • [ 177787-26-7 ]
  • 2-propyl-4-(trifluoromethyl)-1-[5-(3,4,5-trifluorophenyl)-1,2,4-oxadiazol-3-yl]methyl}-1H-indole-5-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With N-ethyl-N,N-diisopropylamine In acetonitrile at 150℃; for 0.5h; Microwave irradiation; 280 Example 280 2-Propyl-4-(trifluoromethyl)-1-[5-(3,4,5-trifluorophenyl)-1,2,4-oxadiazol-3- yl]methyl}-1H-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 3,4,5-trifluorobenzoyl chloride (0.241 g, 1.23 mmol) and N,N-diisopropylethylamine (0.5OmL, 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 0.065 g (45% yield) of pure product: MS (ES) m/z 464 (M+).
  • 5
  • C7H4BrF3Zn [ No CAS ]
  • [ 177787-26-7 ]
  • C14H6F6O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With lithium bromide In tetrahydrofuran at -25 - 20℃; for 16h;
  • 6
  • [ 177787-26-7 ]
  • 3,5-difluoro-4-[bis(2-bromoethyl)-amino]benzoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 78 percent / tetrahydrofuran / 2 h / 0 - 20 °C 2: 37 percent / N,N-dimethyl-acetamide / 84 h / 90 °C 3: Et3N; DMAP / CH2Cl2 / 20 °C 4: 0.40 g / LiBr / acetone / 5 h / Heating 5: 85 percent / trifluoroacetic acid / 0.92 h
  • 7
  • [ 177787-26-7 ]
  • 3,5-difluoro-4-[bis(2-chloroethyl)amino]benzoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 78 percent / tetrahydrofuran / 2 h / 0 - 20 °C 2: 37 percent / N,N-dimethyl-acetamide / 84 h / 90 °C 3: Et3N; DMAP / CH2Cl2 / 20 °C 4: 0.32 g / LiCl / dimethylformamide / 20 °C 5: 85 percent / trifluoroacetic acid / 0.92 h
  • 8
  • [ 177787-26-7 ]
  • 3,5-difluoro-4-[bis(2-iodoethyl)amino]benzoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 78 percent / tetrahydrofuran / 2 h / 0 - 20 °C 2: 37 percent / N,N-dimethyl-acetamide / 84 h / 90 °C 3: Et3N; DMAP / CH2Cl2 / 20 °C 4: NaI / acetone / Heating 5: 73 percent / trifluoroacetic acid / 0.92 h
  • 9
  • [ 177787-26-7 ]
  • [ 863562-22-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 78 percent / tetrahydrofuran / 2 h / 0 - 20 °C 2: 37 percent / N,N-dimethyl-acetamide / 84 h / 90 °C 3: Et3N; DMAP / CH2Cl2 / 20 °C 4: 0.40 g / LiBr / acetone / 5 h / Heating
  • 10
  • [ 177787-26-7 ]
  • [ 863562-18-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 78 percent / tetrahydrofuran / 2 h / 0 - 20 °C 2: 37 percent / N,N-dimethyl-acetamide / 84 h / 90 °C 3: Et3N; DMAP / CH2Cl2 / 20 °C 4: 0.32 g / LiCl / dimethylformamide / 20 °C
  • 11
  • [ 177787-26-7 ]
  • [ 863562-12-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 78 percent / tetrahydrofuran / 2 h / 0 - 20 °C 2: 37 percent / N,N-dimethyl-acetamide / 84 h / 90 °C
  • 12
  • [ 177787-26-7 ]
  • [ 863562-27-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 78 percent / tetrahydrofuran / 2 h / 0 - 20 °C 2: 37 percent / N,N-dimethyl-acetamide / 84 h / 90 °C 3: Et3N; DMAP / CH2Cl2 / 20 °C 4: NaI / acetone / Heating
  • 13
  • [ 177787-26-7 ]
  • 4-[bis-(2-methanesulfonyloxy-ethyl)-amino]-3,5-difluoro-benzoic acid <i>tert</i>-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 78 percent / tetrahydrofuran / 2 h / 0 - 20 °C 2: 37 percent / N,N-dimethyl-acetamide / 84 h / 90 °C 3: Et3N; DMAP / CH2Cl2 / 20 °C
  • 14
  • [ 177787-26-7 ]
  • 3,4,5-Trifluoro-benzoic acid (2R,3R)-2-(3,4-dihydroxy-phenyl)-5,7-dihydroxy-chroman-3-yl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: Et3N 2: H2 / Pd/C
  • 15
  • [ 90433-54-8 ]
  • [ 177787-26-7 ]
  • 7-(3',4',5'-trifluorobenzoyl)-2-(4'-methoxyphenyl)-4-methoxybenzo[b]thiophene [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane for 18h; 1A Improved Benzo[b]thiophene Derivative Syntheses Compound 12A-7-(3',4',5'-trifluorobenzoyl)-2-(4'-methoxyphenyl)-4-methoxybenzo[b]thiophene (see FIG. 15) was synthesized as follows: to a well stirred solution of 2-(4'-methoxyphenyl)-4-methoxybenzo[b]thiophene (0.201 g, 0.74 mmol) and 3,4,5-trifluorobenzoyl chloride (0.288 g, 1.48 mmol) in CH2Cl2 (7 mL) was added AlCl3 (0.304 g, 2.22 mmol) portion-wise over a 15 minute period. After 18 h, water was added, and the product was isolated initially with CH2Cl2 and subsequently by extraction with EtOAc. The organic layers were separately washed sequentially with NaHCO3 and brine and then dried over MgSO4. Purification by flash chromatography (silica gel, 80:20 hexane/EtOAc) afforded benzo[b]thiophene (0.032 g, 0.08 mmol, 10%) as a white solid. Recrystallization (Ethanol/hexane/CH2Cl2) yielded a highly pure crystalline sample. 1H-NMR(CDCl3, 360 MHz) δ7.74 (d, J=8.9 Hz, 2H, ArH), 7.70 (d, J=9.3 Hz, 1H, ArH), 7.68 (s, 1H, ArH), 7.43 (dd, J=7.5, 6.6 Hz, 2H, ArH), 7.00 (d, J=8.9 Hz, 2H, ArH), 6.83 (d, J=8.4 Hz, 1H, ArH), 4.09 (s, 3H, -OCH3), 3.87 (S, 3H, -OCH3). 13C-NMR (CDCl3, 90 MHz) 190.5, 160.1, 159.1, 152.3, 150.0, 146.6, 141.3, 134.4, 132.9, 132.1, 127.9, 126.9, 122.4, 114.5, 114.1, 114.1, 114.0, 113.9, 113.8, 56.0, 55.4. HRMS (EI) M+ calcd for C23H15F3O3S 428.0694 found 428.0620.
  • 16
  • [ 63675-74-1 ]
  • [ 177787-26-7 ]
  • 3-(3',4',5'-trifluorobenzoyl)-2-(4'-methoxyphenyl)-6-methoxybenzo[b]thiophene [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% In dichloromethane for 30h; Heating / reflux; 1A Improved Benzo[b]thiophene Derivative Syntheses Compound 14A-3-(3',4',5'-trifluorobenzoyl)-2-(4'-methoxyphenyl)-6-methoxybenzo[b]thiophene (see FIG. 17) was synthesized as follows. To a well-stirred solution of 2-(4'methoxyphenyl)-6-methoxybenzo[b]thiophene (0.112 g, 0.414 mmol) and 3,4,5-trifluorobenzoyl chloride (0.437 g, 2.271 mmol) in CH2Cl2 (40 ml) was added AlCl3 (0.471 g, 3.532 mmol) portionwise over a 15 min period under reflux conditions. After 30 h, water was added, and the product was isolated initially by extraction with CH2Cl2 and subsequently by extraction with EtOAc. The organic layers were washed separately with brine and then combined and dried over MgSO4. Purification by flash chromatography (silica gel, first with hexanes then with 95:5 hexane/EtOAc) afforded a yellow liquid (0.068 g, 43%). 1H-NMR (CDCl3, 360MHz) d 7.69 (d, J=8.9 Hz, 1H, ArH), 7.37 (d, J=6.7 Hz, 1H, ArH), 7.35 (d, J=6.7 Hz, 1H; ArH), 7.33 (d, J=2.4 Hz, 1H, ArH), 7.26 (d, J=8.8 Hz, 2H, ArH), 7.04 (dd, J=8.9, 2.4 Hz, 1H, ArH), 6.77 (d, J=8.8 Hz, 2H, ArH), 3.90 (s, 3H, OCH3), 3.77 (s, 3H, -OCH3).
  • 17
  • [ 288156-90-1 ]
  • [ 177787-26-7 ]
  • [ 288157-64-2 ]
YieldReaction ConditionsOperation in experiment
99% 68 Example 68; 4-[3-(3,4,5-trifluorobenzamidyl)benzoyl]-1-methylpiperidine Following the example above and beginning with 4-[3-aminobenzoyl]-1-methylpiperidine (25 mg, 0.115 mmol) and 3,4,5-trifluorobenzoyl chloride (30 μL, 0.229 mmol), 42.5 mg (99%) of the title compound were recovered. [00604] MS(m/e): 377(M+1), 375(M-1).
  • 18
  • [ 7580-85-0 ]
  • [ 177787-26-7 ]
  • [ 570407-87-3 ]
YieldReaction ConditionsOperation in experiment
With pyridine; dmap at 0 - 20℃; 98 Reference Example 98 To a solution of 1.52 g of 3,4,5-trifluorobenzoic acid in 15 ml of dichloromethane, 0.92 ml of oxalyl chloride was added under ice cooling, and the mixture was stirred at the same temperature for 30 minutes and at room temperature for 80 minutes. After DMF was added dropwise, the mixture was stirred at room temperature for 1 hour. To the residue obtained by the evaporation of the solvent under reduced pressure, 20 ml of pyridine, 3.40 ml of 2-tert-butoxyethanol, and 1 fold by spatula of DMAP were added 'under ice cooling, and the mixture was stirred at room temperature overnight. After the evaporation of the solvent under reduced pressure, the residue was mixed with saturated NaHCO3 aq. extracted with EtOAc, washed with water and brine, and dried over MgSO4. The solvent was evaporated under reduced pressure to obtain 2.10 g of crude 3,4,5-trifluorobenzoic acid 2-tert-butoxyethyl ester. To a solution of 1.03 g of potassium tert-butoxide in 15 ml of THF, 1.50 ml of 2-tert-butoxyethanol was added, and the mixture was stirred for 40 minutes. The reaction solution was cooled to -78 °C, a solution of 2.10 g of crude 3,4,5-trifluorobenzoic acid 2-tert-butoxyethylester in 5 ml of THF was added thereto, and the mixture was stirred under ice cooling for 1 hour and at room temperature for 30 minutes. The reaction solution was mixed with saturated aqueous ammonium chloride, extracted with EtOAc, and washed with water and brine, and then dried over MgSO4. The residue obtained by the evaporation of the solvent under reduced pressure was purified by silica gel column chromatography (eluent: hexane-EtOAc = 100:1∼20:1) to obtain 2.24 g of 4-(2-tert-butoxyethoxy)-3,5-difluorobenzoic acid 2-tert-butoxyethyl ester.
  • 19
  • [ 109-86-4 ]
  • [ 177787-26-7 ]
  • [ 1342424-26-3 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate at 100℃; for 20h; 139 Reference Example 139 Reference Example 139 To 1.56 g of 3,4,5-trifluorobenzoylchloride, 6.32 ml of 2-methoyethanol and 6.53 g of cesium carbonate were added, and the mixture was stirred at 100 °C for 20 hours.. The reaction solution was mixed with 50 ml of THF and filtered, and the filtrate was evaporated to obtain 4.36 g of colorless solid.. The solid was dissolved in 15 ml of THF, 3.16 ml of 2-methoxyethanol, and 1.35 g of potassium tert-butoxide were added thereto, and the mixture was stirred at room temperature for 4 days.. The reaction solution was mixed with 5% potassium hydrogensulfate aq. and extracted with EtOAc. The organic layer was washed with brine and dried over sodium sulfate, and then the solvent was evaporated to obtain 1.76 g of 3,5-difluoro-4-(2-methoxyethoxy)benzoic acid.
  • 20
  • [ 121602-93-5 ]
  • [ 177787-26-7 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride;N,N-dimethyl-formamide; In dichloromethane; for 1h;Heating / reflux; A mixture of 1 equivalent of a substituted benzoic acid, 3 equivalents of thionyl chloride and [5%] DMF in dichloromethane [(1M)] were heated at reflux temperature for 1 hour and the solvents were removed in vacuo. Dry toluene was added and removed in vacuo. The resulting acid chloride was dissolved in dry THF. Aniline (1.1 equivalents) and of triethylamine (2 equivalents) were added to the reaction mixture at 0-5 [XB0;C] and stirred for further one hour at 0 [XB0;C.] The solvent was removed in vacuo and the crude product was chromatographed (silica [ETOAC-HEXANES)] to give the desired substituted phenyl-N-benzamide.
With oxalyl dichloride; In dichloromethane; at 0 - 20℃; for 1.83333h; To a solution of 1.52 g of <strong>[121602-93-5]3,4,5-trifluorobenzoic acid</strong> in 15 ml of dichloromethane, 0.92 ml of oxalyl chloride was added under ice cooling, and the mixture was stirred at the same temperature for 30 minutes and at room temperature for 80 minutes. After DMF was added dropwise, the mixture was stirred at room temperature for 1 hour. To the residue obtained by the evaporation of the solvent under reduced pressure, 20 ml of pyridine, 3.40 ml of 2-tert-butoxyethanol, and 1 fold by spatula of DMAP were added 'under ice cooling, and the mixture was stirred at room temperature overnight. After the evaporation of the solvent under reduced pressure, the residue was mixed with saturated NaHCO3 aq. extracted with EtOAc, washed with water and brine, and dried over MgSO4. The solvent was evaporated under reduced pressure to obtain 2.10 g of crude <strong>[121602-93-5]3,4,5-trifluorobenzoic acid</strong> 2-tert-butoxyethyl ester. To a solution of 1.03 g of potassium tert-butoxide in 15 ml of THF, 1.50 ml of 2-tert-butoxyethanol was added, and the mixture was stirred for 40 minutes. The reaction solution was cooled to -78 C, a solution of 2.10 g of crude <strong>[121602-93-5]3,4,5-trifluorobenzoic acid</strong> 2-tert-butoxyethylester in 5 ml of THF was added thereto, and the mixture was stirred under ice cooling for 1 hour and at room temperature for 30 minutes. The reaction solution was mixed with saturated aqueous ammonium chloride, extracted with EtOAc, and washed with water and brine, and then dried over MgSO4. The residue obtained by the evaporation of the solvent under reduced pressure was purified by silica gel column chromatography (eluent: hexane-EtOAc = 100:1?20:1) to obtain 2.24 g of 4-(2-tert-butoxyethoxy)-3,5-difluorobenzoic acid 2-tert-butoxyethyl ester.
  • 21
  • [ 62-53-3 ]
  • [ 177787-26-7 ]
  • [ 1274669-24-7 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran at 0 - 5℃; for 1h; Heating / reflux; A mixture of 1 equivalent of a substituted benzoic acid, 3 equivalents of thionyl chloride and [5%] DMF in dichloromethane [(1M)] were heated at reflux temperature for 1 hour and the solvents were removed in vacuo. Dry toluene was added and removed in vacuo. The resulting acid chloride was dissolved in dry THF. Aniline (1.1 equivalents) and of triethylamine (2 equivalents) were added to the reaction mixture at 0-5 [XB0;C] and stirred for further one hour at 0 [XB0;C.] The solvent was removed in vacuo and the crude product was chromatographed (silica [ETOAC-HEXANES)] to give the desired substituted phenyl-N-benzamide.
  • 22
  • [ 851882-63-8 ]
  • [ 177787-26-7 ]
  • {(S)-3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-(3,4,5-trifluoro-phenyl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% Stage #1: (S)-3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidine; 3,4,5-trifluorobenzoyl chloride With triethylamine In dichloromethane at 0 - 20℃; Stage #2: With hydrogenchloride 26 Example 26 {(S)-3-[3-(4-fluoro-phenyl)-[1, 2, 4] oxadiazol-5-yl]-piperidin-1-yl}-(3, 4, 5-trifluoro- phenyl)-methanone The compound was prepared following the procedure described in the Example 13, using 3,4, 5-trifluoro benzoyl chloride as the acyl chloride of choice and S-3- [3- (4- fluoro-phenyl)- [1, 2,4] oxadiazol-5-yl] -piperidine hydrochloride (prepared as described in the Example 12). Yield: 63 % (white solid); mp=139-140°C ; [a] D20= +81° (c=1.0, CHC13) ; LCMS (Tr): 7.67 min (Method A); MS (ES+) gave m/z : 406.1. 1H-NMR (CDC13,336 K, 300 MHz), 8 (ppm): 8.10-8. 01 (m, 2H); 7.20-7. 01 (m, 4H); 4.39-4. 20 (m, 1H) ; 3.92-3. 77 (m, 1H) ; 3.61 (dd, lH) ; 3.42-3. 18 (m, 2H); 2. 38-2. 25 (m, lH); 2.15-1. 85 (m, 2H); 1.77-1. 59 (m, 1H).
  • 23
  • [ 79-37-8 ]
  • [ 121602-93-5 ]
  • [ 177787-26-7 ]
YieldReaction ConditionsOperation in experiment
N,N-dimethyl-formamide; In dichloromethane; <strong>[121602-93-5]3,4,5-Trifluorobenzoic acid</strong> (0.176 g, 1.0 mmol) in dichloromethane (1.5 mL) was treated with a solution of oxalyl chloride (1.5 mL of 2 M in dichloromethane, 3 mmol) and a catalytic amount of N,N-dimethylformamide. The reaction was stirred overnight at ambient temperature. The excess oxalyl chloride was removed in vacuo to afford 3,4,5-trifluorobenzoyl chloride.
  • 24
  • [ 177787-30-3 ]
  • [ 177787-26-7 ]
  • (4-(4-n-pentyl-4-silacyclohexyl)phenyl) trans-3,4,5-trifluorobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
37 Preparation of (4-(4-n-pentyl-4-silacyclohexyl)phenyl) trans-3,4,5-trifluorobenzoate EXAMPLE 37 Preparation of (4-(4-n-pentyl-4-silacyclohexyl)phenyl) trans-3,4,5-trifluorobenzoate The general procedure of Example 26 was repeated using 3,4,5-trifluorobenzoyl chloride and 4-(4-phenyl-4-n-pentyl-4-silacyclohexyl)phenol, thereby obtaining the intended product.
  • 25
  • [ 3326-34-9 ]
  • [ 177787-26-7 ]
  • [ 209540-87-4 ]
YieldReaction ConditionsOperation in experiment
Example 26 Preparation of 5-(3',4',5'-trifluorobenzoylamino)fluorescein (26): 5-Aminofluorescein (100 mg, 0.29 mmol) is reacted with 3,4,5-trifluorobenzoyl chloride (87 mg, 0.45 mmol) at 0 C. under dry nitrogen protection, and worked up according to the procedure of Example 1. Compound 26 is obtained as a brown solid (105 mg, yield: 72%).
  • 26
  • [ 3218-02-8 ]
  • [ 177787-26-7 ]
  • [ 935527-11-0 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In ethyl acetate at 20℃; for 3h; 31 Production Example 31; To 10 ml of ethyl acetate were added 0.50 g of 3,4,5- trifluorobenzoyl chloride, 0.32 g of cyclohexylmethylamine and 0.50 g of triethylamine and the mixture obtained was stirred at room temperature for 3 hours. The reaction mixture was filtered through Celite. The filtrate was concentrated under reduced pressure. Crystals obtained were washed with a mixture of hexane and MTBE to obtain 0.70 g of N-cyclohexylmethyl-3, 4, 5-trifluorobenzamide . N-cyclohexylmethyl-3, 4, 5-trifluorobenzamide : 1H-NMR (CDCl3) δ: 0.92-1.80 (HH, m) , 3.28 (2H, t, J = 6.4 Hz), 6.17 (IH, br s), 7.42 (2H, dd, J = 7.7, 6.5 Hz).To 10 ml of DMF were added 0.50 g of N- cyclohexylmethyl-3, 4 , 5-trifluorobenzamide and 0.15 g of propargyl alcohol and to the mixture obtained was added 100 mg of sodium hydride at 0°C . The mixture obtained was stirred at room temperature for 2 hours. Then, the reaction mixture was concentrated. The residue was subjected to silica gel column chromatography to obtain 0.49 g of N-cyclohexylmethyl-4- (2-propynyloxy) -3, 5- difluorobenzamide (hereinafter, described as the compound 32 of the present invention) represented by the formula: The compound 32 of the present invention:1H-NMR (CDCl3) δ: 0.91-1.31 (5H, m) , 1.51-1.81 (6H, m) , 2.52 (IH, t, J = 2.4 Hz), 3.27 (2H, t, J = 6.5 Hz), 4.87 (2H, d, J = 2.4 Hz), 6.25 (IH, br s) , 7.36 (2H, d, J = 8.7 Hz) .
  • 27
  • [ 870-24-6 ]
  • [ 177787-26-7 ]
  • [ 1109138-72-8 ]
YieldReaction ConditionsOperation in experiment
51% With triethylamine In dichloromethane at 0℃; for 3h; Inert atmosphere;
  • 28
  • [ 6638-79-5 ]
  • [ 177787-26-7 ]
  • [ 226260-00-0 ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: N,O-dimethylhydroxylamine*hydrochloride With triethylamine In dichloromethane at 0℃; Inert atmosphere; Stage #2: 3,4,5-trifluorobenzoyl chloride In dichloromethane at 0 - 20℃; Inert atmosphere;
  • 29
  • [ 155204-28-7 ]
  • [ 177787-26-7 ]
  • [ 1214273-96-7 ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine In dichloromethane at 0 - 20℃;
  • 30
  • [ 108-45-2 ]
  • [ 177787-26-7 ]
  • [ 1270966-04-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrahydrofuran / 20 °C 2: Lawessons reagent / tetrahydrofuran / Reflux
  • 31
  • [ 108-45-2 ]
  • [ 177787-26-7 ]
  • N,N'-(1,3-phenylene)bis(3,4,5-trifluorobenzamide) [ No CAS ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran at 20℃; 5.1.3. General procedure for the synthesis of the dibenzamide derivative 9 and dithiodibenzamide derivatives of set II, III, and IV General procedure: To a solution of 15 mmol appropriate phenylenediamine in 50 ml THF 35 mmol of the adequate benzoyl chloride were added quickly and stirred at room temperature for 2-3 h. Afterwards, the reaction mixture was purged into ice water. The formed solid was filtered off and recrystallized.
  • 32
  • [ 95-54-5 ]
  • [ 177787-26-7 ]
  • [ 1270966-08-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrahydrofuran / 20 °C 2: Lawessons reagent / tetrahydrofuran / Reflux
  • 33
  • [ 95-54-5 ]
  • [ 177787-26-7 ]
  • N,N'-(1,2-phenylene)bis(3,4,5-trifluorobenzamide) [ No CAS ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran at 20℃; 5.1.3. General procedure for the synthesis of the dibenzamide derivative 9 and dithiodibenzamide derivatives of set II, III, and IV General procedure: To a solution of 15 mmol appropriate phenylenediamine in 50 ml THF 35 mmol of the adequate benzoyl chloride were added quickly and stirred at room temperature for 2-3 h. Afterwards, the reaction mixture was purged into ice water. The formed solid was filtered off and recrystallized.
  • 34
  • [ 106-50-3 ]
  • [ 177787-26-7 ]
  • [ 1270965-99-5 ]
YieldReaction ConditionsOperation in experiment
63% In tetrahydrofuran at 20℃; 5.1.3. General procedure for the synthesis of the dibenzamide derivative 9 and dithiodibenzamide derivatives of set II, III, and IV General procedure: To a solution of 15 mmol appropriate phenylenediamine in 50 ml THF 35 mmol of the adequate benzoyl chloride were added quickly and stirred at room temperature for 2-3 h. Afterwards, the reaction mixture was purged into ice water. The formed solid was filtered off and recrystallized.
  • 35
  • [ 106-50-3 ]
  • [ 177787-26-7 ]
  • [ 1270966-01-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrahydrofuran / 20 °C 2: Lawessons reagent / tetrahydrofuran / Reflux
  • 36
  • [ 2257-52-5 ]
  • C14H17N3O2*2ClH [ No CAS ]
  • [ 177787-26-7 ]
  • [ 1262193-95-2 ]
YieldReaction ConditionsOperation in experiment
8% Stage #1: C14H17N3O2*2ClH; 3,4,5-trifluorobenzoyl chloride With triethylamine In toluene for 3h; Reflux; Stage #2: N-isopropylhydrazine In toluene for 3h; Reflux; B.B41 Example B41 Et3N (4.18 ml, 30.1 mmol) was added to a sol. of intermediate 2 (Ig, 3.01 mmol) and 3,4,5-trifluorobenzoylchloride (761 mg, 3.91 mmol) in toluene (q.s.). The r.m. was heated at reflux for 2 h. Subsequently 1 more eq. 3,4,5-trifluorobenzoylchloride was added and the r.m. was refluxed for 1 h. Subsequently, isopropylhydrazine (1.14 g, 15 mmol) was added and the r.m. was refluxed for 3 h. The mixture was cone, under reduced pressure, and the residue was purified by chromatography over silica gel (eluent: DCM/MeOH(NH3) from 100/0 to 95/5). The product fractions were collected and evaporated. Yield: 100 mg of compound 84 (8 %).
  • 37
  • [ 1791-23-7 ]
  • [ 177787-26-7 ]
  • [ 1263864-79-4 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;
  • 38
  • [ 2450-71-7 ]
  • [ 177787-26-7 ]
  • [ 1274141-26-2 ]
YieldReaction ConditionsOperation in experiment
93% With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere;
  • 39
  • [ 177787-26-7 ]
  • [ 1338823-89-4 ]
YieldReaction ConditionsOperation in experiment
With sodium azide In tetrahydrofuran; water for 3h; Reflux;
  • 40
  • [ 89-25-8 ]
  • [ 177787-26-7 ]
  • [ 1356140-53-8 ]
YieldReaction ConditionsOperation in experiment
73.2% Stage #1: edaravone With calcium hydroxide In 1,4-dioxane at 60℃; for 0.333333h; Stage #2: 3,4,5-trifluorobenzoyl chloride In 1,4-dioxane for 0.5h; Reflux;
  • 41
  • [ 4314-38-9 ]
  • [ 177787-26-7 ]
  • C15H2F20N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In acetone at 20℃;
  • 42
  • [ 4314-38-9 ]
  • [ 177787-26-7 ]
  • C15H4F18N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In acetone at 20℃; for 1h;
  • 43
  • [ 177787-26-7 ]
  • [ 919489-99-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate / acetone / 20 °C 2: 180 °C / Neat (no solvent)
  • 44
  • [ 177787-26-7 ]
  • [ 1370734-20-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 1 h / 20 °C 2: 180 °C / Neat (no solvent) 3: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 20 °C
  • 45
  • [ 177787-26-7 ]
  • [ 1370734-22-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 20 °C 2: 180 °C / Neat (no solvent) 3: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 20 °C
  • 46
  • [ 177787-26-7 ]
  • [ 1370734-25-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: potassium carbonate / acetone / 1 h / 20 °C 2: 180 °C / Neat (no solvent) 3: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 20 °C 4: water; potassium hydroxide / tetrahydrofuran / 2 h / 20 °C
  • 47
  • [ 177787-26-7 ]
  • [ 1370734-27-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: potassium carbonate / acetone / 20 °C 2: 180 °C / Neat (no solvent) 3: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 20 °C 4: water; potassium hydroxide / tetrahydrofuran / 2 h / 20 °C
  • 48
  • [ 177787-26-7 ]
  • [ 1370734-23-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate / acetone / 1 h / 20 °C 2: 180 °C / Neat (no solvent)
  • 49
  • [ 1217428-98-2 ]
  • [ 177787-26-7 ]
  • C11H9F3N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In acetone at 20℃; for 1h; 4.6. General procedure for the preparation of compounds 13a-e General procedure: A 10% excess of the appropriate fluorinated aroyl chlorides 10a-e (4.4 mmol) was added to a solution of compound 12 (0.52 g, 4.0 mmol) in acetone (20 mL) together with K2CO3 (0.60 g, 4.4 mmol). The mixture was stirred at room temperature for 1 h after which the solvent was removed under reduced pressure. The residue was treated with water and the solid collected by filtration and heated, without any previous purification, at 180 °C for 30 min in a sealed tube. Chromatography of the residue yielded the corresponding oxadiazole compounds 13a-e.
  • 50
  • 2-acetamido-1-aminoacetaldoxime [ No CAS ]
  • [ 177787-26-7 ]
  • C11H10F3N3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In acetone at 20℃; for 1h; 4.4. General procedure for the preparation of compounds 9 and 11a-e General procedure: Either benzoyl chloride or fluorinated aroyl chlorides 10a-e (2.2 mmol) were added to a solution of 8 (0.26 g; 2 mmol) in Acetone (20 mL) containing also K2CO3 (0.30 g, 2.2 mmol). The mixture was stirred at room temperature for 1 h after which the solvent was removed under reduced pressure. The residue was treated with water and the solid precipitate was collected by filtration. The O-acylamidoxime so formed was heated, without any further purification, at 170 °C for 5 min in a sealed tube. The crude material obtained was purified by column chromatography to give the desired products 1,2,4-oxadiazoles 9 and 11a-e.
  • 51
  • [ 177787-26-7 ]
  • [ 1284680-63-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate / acetone / 1 h / 20 °C 2: 0.5 h / 180 °C / Sealed tube; Neat (no solvent)
  • 52
  • [ 177787-26-7 ]
  • [ 1370025-79-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 1 h / 20 °C 2: 0.5 h / 180 °C / Sealed tube; Neat (no solvent) 3: ammonia / methanol / 0.5 h / 20 °C
  • 53
  • [ 177787-26-7 ]
  • [ 1370025-84-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: potassium carbonate / acetone / 1 h / 20 °C 2: 0.5 h / 180 °C / Sealed tube; Neat (no solvent) 3: ammonia / methanol / 0.5 h / 20 °C 4: N,N-dimethyl-formamide / 1 h / Reflux
  • 54
  • N,N'-di(n-hexyl)-2,6-bis(tri(n-butyl)stannyl) naphthalene-1,8:4,5-bis(dicarboximide) [ No CAS ]
  • [ 177787-26-7 ]
  • C40H32F6N2O6*FH [ No CAS ]
YieldReaction ConditionsOperation in experiment
9.2% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In toluene at 100℃; Inert atmosphere;
  • 55
  • C15H33N7O3*C2HF3O2 [ No CAS ]
  • [ 177787-26-7 ]
  • [ 1410800-23-5 ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: C15H33N7O3*C2HF3O2 With triethylamine In dichloromethane at 20℃; for 0.25h; Inert atmosphere; Stage #2: 3,4,5-trifluorobenzoyl chloride In dichloromethane at 20℃; for 25h; Inert atmosphere;
  • 56
  • [ 177787-26-7 ]
  • [ 796072-79-2 ]
  • 2-(3'-tert-butyldimethylsiloxy-4'-methoxyphenyl)-3-(3'',4'',5''-trifluorobenzoyl)-6-methoxyindole [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% In 1,2-dichloro-benzene at 160℃; for 12h; 4.1.12 2-(3′-tert-Butyldimethylsiloxy-4′-methoxyphenyl)-3-(3″,4″,5″-trifluorobenzoyl)-6-methoxyindole (16) To a solution of compound 5 (0.61g, 1.59mmol) in o-dichlorobenzene (10mL) was added 3,4,5-trifluorobenzoylchloride (3.12mL, 2.38mmol). The reaction mixture was heated to reflux at 160°C for 12h. The o-dichlorobenzene was removed by simple distillation, and the resulting dark colored solid was subjected to flash chromatography using a prepacked 100g silica column [solvent (A) EtOAc; solvent (B) hexanes; gradient: 7%A/93%B (4 CV), 7%A/93%B→60%A/40%B (10 CV), 60%A/40%B (5.5 CV); flow rate: 40mL/min; monitored at 254 and 280nm] resulting in TBS-indole 16 as a white powder (0.70g, 1.29mmol, 81%, Rf=0.48 (50:50 hexanes:EtOAc)). 1H NMR (CDCl3, 500MHz): δ 8.44 (br s, 1H, NH), 7.95 (d, J=9.0Hz, 1H, ArH), 7.25 (m, 2H, ArH), 6.94 (dd, J=8.5Hz, 2.5Hz, 1H, ArH), 6.91 (d, J=2.0Hz, 1H, ArH), 6.83 (dd, J=8.0Hz, 2.0Hz, 1H, ArH), 6.79 (d, J=2.0Hz, 1H, ArH), 6.70 (d, J=8.5Hz, 1H, ArH), 3.87 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 0.97 (s, 9H, C(CH3)3), 0.09 (s, 6H, Si(CH3)2). 13C NMR (CDCl3, 125MHz): δ 189.1, 157.7, 152.1, 150.6 (ddd, JC-F=250.0Hz, 10.0Hz, 3.1Hz), 145.4, 143.5, 141.8 (dt, JC-F=255.9Hz, 15.5Hz), 136.5, 135.6 (d, JC-F=3.9Hz), 124.4, 123.2, 122.8, 121.4, 121.6, 114.1 (dd, JC-F=16.9Hz, 5.1Hz), 112.3, 112.2, 112.0, 94.8, 55.9, 55.6, 25.7, 18.5, -4.8. 19F NMR (CDCl3, 470MHz): δ -134.0 (dd, J=21.2Hz, 7.5Hz, 2F, ArF), -155.6 (tt, J=20.2Hz, 6.6Hz, 1F, ArF). HPLC: 21.32min, purity at 254nm >99%. HRMS (ESI+): m/z calculated for C29H30F3NNaO4Si [M+Na]+ 564.1788, found 564.1786.
  • 57
  • [ 177787-26-7 ]
  • bis[bis(3,4,5-trifluorobenzoyl)methanido]copper(II) [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / 1,1,2,2-tetrachloroethane / 1 h / 45 °C / Inert atmosphere 1.2: 13 h / 25 - 35 °C / Inert atmosphere 2.1: sodium methylate / methanol / 2 h / 20 °C
  • 58
  • [ 108-05-4 ]
  • [ 177787-26-7 ]
  • bis(3,4,5-trifluorobenzoyl)methane [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% Stage #1: 3,4,5-trifluorobenzoyl chloride With aluminum (III) chloride In 1,1,2,2-tetrachloroethane at 45℃; for 1h; Inert atmosphere; Stage #2: vinyl acetate at 25 - 35℃; for 13h; Inert atmosphere;
  • 59
  • [ 58039-64-8 ]
  • [ 177787-26-7 ]
  • (2-phenethylmorpholino)(3,4,5-trifluorophenyl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1h;
  • 60
  • C24H34N4O6 [ No CAS ]
  • [ 177787-26-7 ]
  • 2,2-di-tert-butoxycarbonylamino-5-[4-(3,4,5-trifluorobenzoylamino)phenyl]imidazole-1-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane
With potassium phosphate In tetrahydrofuran at 0 - 25℃; for 16h;
  • 61
  • [ 6038-49-9 ]
  • [ 177787-26-7 ]
  • C23H14ClF3N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
  • 62
  • [ 15987-90-3 ]
  • [ 177787-26-7 ]
  • C25H19F3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
  • 63
  • C19H20N2O2 [ No CAS ]
  • [ 177787-26-7 ]
  • C26H21F3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
  • 64
  • C17H14N2O3 [ No CAS ]
  • [ 177787-26-7 ]
  • C24H15F3N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
  • 65
  • C17H15FN2O2 [ No CAS ]
  • [ 177787-26-7 ]
  • C24H16F4N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
  • 66
  • C17H15ClN2O2 [ No CAS ]
  • [ 177787-26-7 ]
  • C24H16ClF3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
  • 67
  • C18H18N2O2 [ No CAS ]
  • [ 177787-26-7 ]
  • V(524)U0683 [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Synthesis of VU6000181 Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
  • 68
  • C17H15FN2O2 [ No CAS ]
  • [ 177787-26-7 ]
  • C24H16F4N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
  • 69
  • C17H15ClN2O2 [ No CAS ]
  • [ 177787-26-7 ]
  • C24H16ClF3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
  • 70
  • C18H18N2O2 [ No CAS ]
  • [ 177787-26-7 ]
  • C25H19F3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
  • 71
  • [ 821-41-0 ]
  • [ 177787-26-7 ]
  • hex-5-en-1-yl 3,4,5-trifluorobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; Alkenes 2b-e,g,h,j; General Procedure General procedure: To a 100 mL flask charged with hex-5-en-1-ol (0.50 g, 5.0 mmol), Et3N (1.8 g, 18.0 mmol), and CH2Cl2 (25 mL) was added the appropriate acyl chloride (6 mmol) in CH2Cl2 (ca. 5 mL) at 0 °C. The reaction mixture was vigorously stirred overnight at r.t. Sat. aq NaHCO3 (20 mL) was added and the mixture was stirred at r.t. for 20 min. The organic layer was separated and the aqueous layer was extracted with CH2Cl2(2 × 20 mL). The combined organic extracts were washed with brine, dried (Na2SO4), and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel (eluent: PE-EtOAc, 15 to 10:1 v/v) to provide the corresponding product.
  • 72
  • [ 177787-26-7 ]
  • 8,8,8-trifluoro-5-iodooctyl 3,4,5-trifluorobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 2: tris[2-phenylpyridinato-C2,N]iridium(III); N-ethyl-N,N-diisopropylamine / acetonitrile / 24 h / 20 °C / Inert atmosphere; Schlenk technique; Irradiation
  • 73
  • [ 1267986-38-8 ]
  • [ 177787-26-7 ]
  • [ 1267987-33-6 ]
YieldReaction ConditionsOperation in experiment
54% With triethylamine In dichloromethane at 0 - 20℃; for 0.5h; Inert atmosphere; 62 Synthesis of 4-chloro-N- (3,4,5-trifluorobenzoyl)deacetyl colchicine 4-chlorodeacetyl colchicine (50 mg, 0.128 mmol) was dissolved in dichloromethane (2 mL) under argon atmosphere, and cooled at 0 degree C. Triethylamine (19 mul, 0.128 x 1.1mmol) and 3,4,5-trifluorobenzoylchloride (17 mul, 0.128 x 1 mmol) were added there, and stirred at room temperature for 30 minutes. Water was added and the reaction mixture was quenched, extracted with saturated sodium bicarbonate solution and chloroform. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was purified by Silica gel chromatography(Biotage Isolera One and SNAP10 g, methanol/chloroform) to obtain title compound (a reddish brown solid, 38 mg, 0.069 mmol, 54%) .
  • 74
  • [ 2576-47-8 ]
  • [ 177787-26-7 ]
  • [ 1109138-92-2 ]
YieldReaction ConditionsOperation in experiment
79% Stage #1: 2-bromoethylamine hydrobromide With triethylamine In toluene for 0.0833333h; Inert atmosphere; Stage #2: 3,4,5-trifluorobenzoyl chloride In toluene Inert atmosphere; Reflux;
  • 75
  • [ 99-92-3 ]
  • [ 177787-26-7 ]
  • N-(4-acetylphenyl)-3,4,5-trifluorobenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% With potassium carbonate In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; General Procedure General procedure: The acid chlorides 25 (1 mmol) were suspended in dry THF (5 mL) under argon, 4`-aminoacetophenone (135 mg, 1 mmol) and K2CO3 (68 mg, 0.5 mmol) were added and the mixture was stirred at room temperature for one hour. The solvent was evaporated under reduced pressure. Aqueous HCl (0.5 M, 15 mL) was added, and the solution was extracted with ethyl acetate (30 mL). The crude residue obtained after evaporation of solvent was purified by silica gel flash chromatography using hexane-ethyl acetate (1:1) or by crystallization from 70% methanol to afford the desired product.
  • 76
  • [ 177787-26-7 ]
  • N-{4-[1-(2-carbamimidoylhydrazono)ethyl]phenyl}-3,4,5-trifluorobenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate / tetrahydrofuran / 1 h / 20 °C / Inert atmosphere 2: lithium chloride / ethanol / Reflux
  • 77
  • [ 773873-72-6 ]
  • [ 177787-26-7 ]
  • 78
  • [ 578-66-5 ]
  • [ 177787-26-7 ]
  • C22H11F3N2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 0 - 20 °C 2: tetra-(n-butyl)ammonium iodide; cesium fluoride; copper diacetate; oxygen / N,N-dimethyl-formamide; acetonitrile / 12 h / 80 °C / Sealed tube
  • 79
  • [ 578-66-5 ]
  • [ 177787-26-7 ]
  • N-(3,4,5-trifluorobenzoyl)-8-quinolinamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane at 0 - 20℃;
  • 80
  • [ 80691-81-2 ]
  • [ 177787-26-7 ]
  • diethyl 2,5-bis(3,4,5-trifluorobenzamido)thiophene-3,4-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With pyridine at 0 - 20℃; for 4h;
Same Skeleton Products
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