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Chemical Structure| 2417720-65-9 Chemical Structure| 2417720-65-9

Structure of 2417720-65-9

Chemical Structure| 2417720-65-9

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Product Details of [ 2417720-65-9 ]

CAS No. :2417720-65-9
Formula : C18H11F3O2
M.W : 316.27
SMILES Code : O=C(O)C1=CC=C2C(C3=CC=C(C(F)(F)F)C=C3)=CC=CC2=C1
English Name :5-(4-(Trifluoromethyl)phenyl)-2-naphthoic acid
MDL No. :MFCD35206329

Safety of [ 2417720-65-9 ]

Application In Synthesis of [ 2417720-65-9 ]

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

  • Downstream synthetic route of [ 2417720-65-9 ]

[ 2417720-65-9 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 2417720-65-9 ]
  • [ 2417717-64-5 ]
YieldReaction ConditionsOperation in experiment
27.3% Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With thionyl chloride at 80℃; for 2h; Stage #2: With SULFAMIDE; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 15℃; for 16h; 29.2 Step 2: N-sulfamoyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide A solution of compound 29-2 (80 mg, 0.25 mmol, 1 eq ) and SOCh (6.02 g, 50.59 mmol, 3.7 mL, 200 eq) was heated at 80 °C for 2 h and then concentrated under vacuum to give a residue, which was quickly dissolved in DCM (3 mL). The resulting solution was drop-wise added to a solution of sulfamide (48.6 mg, 0.51 mmol, 30 uL, 2 eq) and DIPEA (81.7 mg, 0.63 mmol, 0.1 mL, 2.5 eq) in DCM (3 mL) at 0°C. Then the resulting mixture was stirred at 15 °C for 16 hr. LCMS showed no starting material was remained and 53% of desired product was detected. The mixture was quenched with 1 mL of water and then concentrated to give a residue. The residue was purified by prep-HPLC to give the title compound (28.1 mg, 69 umol, 27.3% yield) as a white solid. LCMS (ESI): RT = 1.615 min, mass calc for C18H13F3N2O3S 394.06, m/z found 395.0 (0813) [M+H]+. NMR (400MHz, DMSO-d6) d 12.08 (s, 1H), 8.70 (d, 7= 1.3 Hz, 1H), 8.36 (s, 1H), 8.16 (d, J= 8.3 Hz, 1H), 7.99 - 7.92 (m, 3H), 7.85 (d, J= 9.0 Hz, 1H), 7.78 - 7.71 (m, 3H), 7.67 - 7.56 (m, 3H).
  • 2
  • [ 2417720-65-9 ]
  • [ 2417718-25-1 ]
  • [ 2417718-26-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; HATU / dichloromethane / 1 h / 25 °C 1.2: 1 h / 25 °C 2.1: Resolution of racemate
  • 3
  • [ 2417720-65-9 ]
  • [ 2417718-63-7 ]
  • [ 2417718-64-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 1 h / 25 °C 1.2: 15 h / 25 °C 2.1: ammonium hydroxide; copper(I) oxide / ethylene glycol / 16 h / 70 °C / Sealed tube
  • 4
  • [ 2417720-65-9 ]
  • [ 765-30-0 ]
  • [ 2417717-90-7 ]
YieldReaction ConditionsOperation in experiment
41.1% Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With triethylamine; HATU In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: Cyclopropylamine In N,N-dimethyl-formamide at 25℃; for 1.5h; 55 Example 55: N-cyclopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide (Compound 55) To a mixture of compound 55-1 (0.05 g, 0.15 mmol, 1 eq) in DMF (2 mL) was added HATU (120.2 mg, 0.31 mmol, 2 eq) and Et3N (47.9 mg, 0.47 mmol, 66 uL, 3 eq). The mixture was stirred for 0.5 hrs at 25 °C. Then cyclopropanamine (18 mg, 0.31 mmol, 21.9 uL, 2 eq) was added to the mixture. The mixture was stirred for 1.5 hrs at 25 °C. LCMS showed the reaction was complete. The mixture was quenched by H20 (30 mL), and the mixture was extracted with EA (20 mL*3). The combined organic phase was washed with brine (20 mL*3), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by prep-HPLC. The title compound (23 mg, 64.9 umol, 41.1% yield) was obtained as a white solid. LCMS (ESI): RT = 0.854 min, mass calc for: C2IHI6F NO 355.35, m/z found 355.9 [M+H]+; NMR (400 MHz, DMSO-d6) d 8.67 (br d, J= 3.5 Hz, 1H), 8.52 (s, 1H), 8.11 (br d, J= 8.0 Hz, 1H), 7.92 (br d, J = (0931) 8.5 Hz, 3H), 7.83 - 7.66 (m, 4H), 7.58 (br d , J= 6.8 Hz, 1H), 2.92 (td, J= 3.5, 7.0 Hz, 1H), 0.80 - 0.68 (m, 2H), 0.63 (br d, J= 3.0 Hz, 2H). .
  • 5
  • [ 80506-64-5 ]
  • [ 2417720-65-9 ]
  • [ 2417717-92-9 ]
YieldReaction ConditionsOperation in experiment
14.4% Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With triethylamine; HATU In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: 2-(2-methoxyethoxy)ethanamine In N,N-dimethyl-formamide at 25℃; for 1.5h; 57 Example 57 : N-(2-(2-methoxyethoxy)ethyl)-5-(4-(trifluoromethyl)phenyl)-2-naphthamide (Compound 57) To a mixture of compound 57-1 (0.05 g, 0.15 mmol, 1 eq) in DMF (2 mL) was added HATLT (120.2 mg, 0.31 mmol, 2 eq) and Et3N (47.9 mg, 0.47 mmol, 66.0 uL, 3 eq). The mixture was stirred for 0.5 hrs at 25 °C. Then 2-(2-methoxyethoxy)ethanamine (37.6 mg, 0.31 mmol, 2 eq) was added to the mixture. The mixture was stirred for 1.5 hrs at 25 °C. LCMS showed the reaction was complete. The mixture was quenched by H20 (30 mL), and the mixture was extracted with EA (20 mL*3). The combined organic phase was washed with brine (20 mL*3), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by prep-HPLC. The title compound (9.56 mg, 22.9 umol, 14.4% yield) was obtained as a white solid. LCMS (ESI): RT = 0.843 min, mass calc for: C23H22F3N03 417.42, m/z found 440.0 [M+Na]+; NMR (400 MHz, DMSO-r) d 8.75 (t, J= 5.8 Hz, 1H), 8.59 - 8.55 (m, 1H), 8.12 (d, J= 8.3 Hz, 1H), 7.96 - 7.90 (m, 3H), 7.83 - 7.68 (m, 4H), 7.60 (d, J= 7.0 Hz, 1H), 3.61 - 3.54 (m, 4H), 3.52 - 3.44 (m, 4H), 3.24 (s, 3H).
  • 6
  • [ 2417720-65-9 ]
  • [ 109-85-3 ]
  • [ 2417717-93-0 ]
YieldReaction ConditionsOperation in experiment
35.7% Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With triethylamine; HATU In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: 2-methoxyethylamine In N,N-dimethyl-formamide at 25℃; for 1.5h; 58 Example 58: N-(2-methoxyethyl)-5-(4-(trifluoromethyl)phenyl)-2-naphthamide (Compound 58) To a mixture of compound 58-1 (0.05 g, 0.15 mmol, 1 eq) in DMF (2 mL) was added HATU (120.2 mg, 0.31 mmol, 2 eq) and Et3N (47.9 mg, 0.47 mmol, 66.0 uL, 3 eq). The mixture was stirred for 0.5 hrs at 25 °C. Then 2-methoxyethanamine (23.7 mg, 0.31 mmol, 27.4 uL, 2 eq) was added to the mixture. The mixture was stirred for 1.5 hrs at 25 °C. LCMS showed the reaction was complete. The mixture was quenched by H20 (30 mL), and the mixture was extracted with EA (20 mL*3). The combined organic phase was washed with brine (20 mL*3), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by prep-HPLC. The title compound (21.1 mg, 56.5 umol, 35.7% yield) was obtained as a white solid. LCMS (ESI): RT = 0.840 min, mass calc for: C2IHI8F N02 373.37, m/z found 373.9 [M+H]+; 1 H NMR (0940) (400MHz, CD OD) d 8.49 (s, 1H), 8.08 (d, J= 8.3 Hz, 1H), 7.91 - 7.83 (m, 4H), 7.74 - 7.65 (m, 3H), 7.58 (dd, j= 1.0, 7.0 Hz, 1H), 3.64 (s, 4H), 3.42 (s, 3H).
  • 7
  • [ 2417720-65-9 ]
  • [ 255735-88-7 ]
  • [ 2417721-51-6 ]
YieldReaction ConditionsOperation in experiment
53.5% Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With triethylamine; HATU In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: [(2R)-2-aminopropyl]carbamic acid,1,1-dimethylethyl ester In N,N-dimethyl-formamide at 25℃; for 2h; 59.1 Step 1: tert-butyl (2-(5-(4-(trifluoromethyl)phenyl)-2-naphthamido)propyl)carbamate To a mixture of compound 59-1 (0.1 g, 0.31 mmol, 1 eq) in DMF (10 mL) was added HATU (240.4 mg, 0.63 mmol, 2 eq) and Et3N (159.9 mg, 1.58 mmol, 0.22 mL, 5 eq). The mixture was stirred for 0.5 hrs at 25 °C. Then tert-butyl N-(2-aminopropyl)carbamate (66.1 mg, 0.37 mmol, 1.2 eq) was added to the mixture. The mixture was stirred for 1.5 hrs at 25 °C. LCMS showed the reaction was complete. The mixture was quenched by H20 (30 mL), and the mixture was extracted with EA (20 mL*3). The combined organic phase was washed with brine (20 mL*3), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate = 50/1 to 1 : 1). Compound 59-2 (0.08 g, 0.16 mmol, 53.5% yield) was obtained as a yellow solid.
  • 8
  • [ 2749-11-3 ]
  • [ 2417720-65-9 ]
  • [ 2417718-19-3 ]
YieldReaction ConditionsOperation in experiment
69.8% Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 25℃; for 1h; Stage #2: (S)-Alaninol In dichloromethane at 25℃; for 1h; 79 Example 79: (S)-N-(l-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenyl)-2-naphthamide (Compound 84) The mixture of compound 84-1 (60 mg, 0.18 mmol, 1 eq), HATU (108.2 mg, 0.28 mmol, 1.5 eq) and DIEA (73.5 mg, 0.56 mmol, 99.1 uL, 3 eq) in DCM (3 mL) was stirred at 25 °C for 1 hr. Then (2S)-2-aminopropan-l-ol (14.2 mg, 0.18 mmol, 14.7 uL, 1 eq) was added at the mixture and the mixture was stirred at 25 °C for another 1 hr. LC-MS showed the desired compound was detected. The reaction mixture was diluted with H20 (10 mL) and the mixture was extracted with EA (15 mL * 3). The combined organic phase was washed with brine (10 mL*3), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by prep-HPLC. The title compound (50 mg, 0.13 mmol, 69.8% yield) was obtained as white solid. LCMS (ESI): RT = 0.931 min, mass calcd for C2IHI8F3N02 373.37, m/z found 374.1 [M+H]+, NMR (400 MHz, DMSO-de) d 8.57 (d, J= 1.5 Hz, 1H), 8.34 (d, J= 8.0 Hz, 1H), 8.12 (d, 7= 8.3 Hz, 1H), 7.96 - 7.90 (m, 3H), 7.81 (d, j= 8.8 Hz, 1H), 7.78 - 7.67 (m, 3H), 7.62 - 7.56 (m, 1H), 4.12 - 4.04 (m, 1H), 3.52 (br dd, J= 5.9, 10.7 Hz, 1H), 2.45 (br s, 1H), 1.18 (d, J= 6.8 Hz, 3H).
  • 9
  • [ 35320-23-1 ]
  • [ 2417720-65-9 ]
  • [ 2417718-20-6 ]
YieldReaction ConditionsOperation in experiment
62.3% Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 25℃; for 1h; Stage #2: (R)-2-aminopropan-1-ol In dichloromethane at 25℃; for 1h; 80 Example 80: (R)-N-(l-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenyl)-2-naphthamide (Compound 85) The mixture of compound 85-1 (70 mg, 0.22 mmol, 1 eq), HATU (126.2 mg, 0.33 mmol, 1.5 eq) and DIEA (85.8 mg, 0.66 mmol, 0.11 mL, 3 eq) in DCM (3 mL) was stirred at 25 °C for 1 hr. Then 2-aminopropan-l-ol (19.9 mg, 0.26 mmol, 21.1 uL, 1.2 eq) was added at the mixture and the mixture was stirred at 25 °C for another 1 hr. LC-MS showed the desired compound was detected. The reaction mixture was diluted with H20 (10 mL) and the mixture was extracted with EA (10 mL * 3). The combined organic phase was washed with brine (10 mL*3), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by prep-HPLC. The title compound (52 mg, 0.13 mmol, 62.3% yield) was obtained as white solid. LCMS (ESI): (1050) RT = 0.924 min, mass calcd for C2IHI8F3N02 373.37, m/z found 374.1 [M+H]+, NMR (400 MHz, DMSO-de) d 8.57 (s, 1H), 8.34 (d, J= 8.0 Hz, 1H), 8.11 (s, 1H), 7.96 - 7.90 (m, 3H), 7.81 (d, J= 8.8 Hz, 1H), 7.76 - 7.67 (m, 3H), 7.59 (d, J= 6.5 Hz, 1H), 4.11 - 4.03 (m, 1H), 4.12 (s, 1H), 3.57 - 3.47 (m, 1H), 3.52 (dd, J= 5.8, 10.5 Hz, 1H), 3.41 (br s, 1H), 1.18 (d, J= 6.8 Hz, 3H).
  • 10
  • [ 2417720-65-9 ]
  • [ CAS Unavailable ]
  • [ 2417718-21-7 ]
YieldReaction ConditionsOperation in experiment
45.2% Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 25℃; for 1h; Stage #2: ethanolamine In dichloromethane at 25℃; for 1h; 81 Example 81: N-(2-hydroxyethyl)-5-(4-(trifluoromethyl)phenyl)-2-naphthamide (Compound The mixture of compound 86-1 (70 mg, 0.22 mmol, 1 eq), HATU (126.2 mg, 0.33 mmol, 1.5 eq) and DIEA (85.8 mg, 0.66 mmol, 0.11 mL, 3 eq) in DCM (2 mL) was stirred at 25 °C for 1 hr , Then 2-aminoethanol (16.2 mg, 0.26 mmol, 16.0 uL, 1.2 eq) was added at the mixture and the mixture was stirred for another 1 hr. LC-MS showed the desired compound was detected. The reaction mixture was diluted with H20 (10 mL) and the mixture was extracted with EA (10 mL * 3). The combined organic phase was washed with brine (10 mL*3), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by prep-HPLC. The title compound (36 mg, 0.10 mmol, 45.2% yield) was obtained as white solid. LCMS (ESI): RT = 0.898 min, mass calcd for C HieFsNCL 359.34, m/z found 360.1 [M+H]+, NMR (400 MHz, DMSO-d6) d 8.67 (br t, J= 5.5 Hz, 1H), 8.58 (d, J= 1.5 Hz, 1H), 8.12 (d, J= 8.3 Hz, 1H), 7.98 - 7.89 (m, 3H), 7.81 (d, J= 8.8 Hz, 1H), 7.77 - 7.67 (m, 3H), 7.59 (dd, J= 1.0, 7.0 Hz, 1H), 4.78 (br s, 1H), 3.61 - 3.51 (m, 2H), 3.45 - 3.39 (m, 2H).
  • 11
  • [ 42088-91-5 ]
  • [ 2417720-65-9 ]
  • [ 2417720-80-8 ]
YieldReaction ConditionsOperation in experiment
72.9% Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 25℃; for 1h; Stage #2: 2-aminoethylpyridine In dichloromethane at 25℃; for 1h; 84.1 Step 1 : N-(l-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenyl)-2-naphthamide The mixture of compound 90-1 (200 mg, 0.63 mmol, 1 eq ), HATU (360.6 mg, 0.94 mmol, 1.5 eq) and DIEA (326.9 mg, 2.53 mmol, 0.44 mL, 4 eq) in DCM (3 mL) was stirred at 25 °C for 1 hr. Then l-(2-pyridyl)ethanamine (92.7 mg, 0.75 mmol, 1.2 eq) was added to the mixture and the mixture was stirred at 25 °C for another 1 hr. LC-MS showed the desired compound was detected. The reaction mixture was diluted with H20 (10 mL) and the mixture was extracted with EA (10 mL * 3). The combined organic phase was washed with brine (10 mL*2), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate = 1/0 to 1 : 1). Compound 90-2 (200 mg, 0.46 mmol, 72.9% yield) was obtained as yellow oil
72.9 % Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 25℃; Stage #2: 2-aminoethylpyridine In dichloromethane at 25℃; 7.1 Step 1: N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenyl)-2-naphthamide The mixture of compound 90-1 of WO2020/097389A1 (200 mg, 0.63 mmol, 1 eq), HATU (360.6 mg, 0.94 mmol, 1.5 eq) and DIEA (326.9 mg, 2.53 mmol, 0.44 mL, 4 eq) in DCM (3 mL) was stirred at 25 °C for 1 hr. Then 1-(2-pyridyl)ethanamine (92.7 mg, 0.75 mmol, 1.2 eq) was added to the mixture and the mixture was stirred at 25 °C for another 1 hr. LC-MS showed the desired compound was detected. The reaction mixture was diluted with H2O (10 mL) and the mixture was extracted with EA (10 mL * 3). The combined organic phase was washed with brine (10 mL*2), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate = 1/0 to 1:1). Compound 90-2 of WO2020/097389A1 (200 mg, 0.46 mmol, 72.9% yield) was obtained as yellow oil.
72.9 % Stage #1: 5-(4-(trifluoromethyl)phenyl)-2-naphthoic acid With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 25℃; Stage #2: 2-aminoethylpyridine In dichloromethane at 25℃; 7.1 Step 1: N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenyl)-2-naphthamide The mixture of compound 90-1 of WO2020/097389A1 (200 mg, 0.63 mmol, 1 eq), HATU (360.6 mg, 0.94 mmol, 1.5 eq) and DIEA (326.9 mg, 2.53 mmol, 0.44 mL, 4 eq) in DCM (3 mL) was stirred at 25 °C for 1 hr. Then 1-(2-pyridyl)ethanamine (92.7 mg, 0.75 mmol, 1.2 eq) was added to the mixture and the mixture was stirred at 25 °C for another 1 hr. LC-MS showed the desired compound was detected. The reaction mixture was diluted with H2O (10 mL) and the mixture was extracted with EA (10 mL * 3). The combined organic phase was washed with brine (10 mL*2), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate = 1/0 to 1:1). Compound 90-2 of WO2020/097389A1 (200 mg, 0.46 mmol, 72.9% yield) was obtained as yellow oil.
 

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