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Chemical Structure| 1242137-15-0 Chemical Structure| 1242137-15-0
Chemical Structure| 1242137-15-0

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Enzalutamide carboxylic acid is an inactive metabolite of Enzalutamide, an androgen receptor (AR) antagonist widely used in prostate cancer research.

Synonyms: MDV3100 carboxylic acid

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Details of Enzalutamide carboxylic acid

CAS No. :1242137-15-0
Formula : C20H13F4N3O3S
M.W : 451.39
SMILES Code : S=C1N(C(C(C)(C)N1C2=CC(F)=C(C(O)=O)C=C2)=O)C3=CC(C(F)(F)F)=C(C#N)C=C3
Synonyms :
MDV3100 carboxylic acid
English Name :4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorobenzoic acid
MDL No. :MFCD28411442
InChI Key :MECDPCCFIDQBBP-UHFFFAOYSA-N
Pubchem ID :46898522

Safety of Enzalutamide carboxylic acid

Application In Synthesis of Enzalutamide carboxylic acid

* 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 [ 1242137-15-0 ]

[ 1242137-15-0 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 1332524-01-2 ]
  • [ 143782-23-4 ]
  • [ 1242137-15-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: dimethyl sulfoxide; Isopropyl acetate / 17.5 h / 83 - 84 °C 2: hydrogenchloride / water / 48 h / 120 °C
  • 2
  • [ 1332524-02-3 ]
  • [ 143782-23-4 ]
  • [ 1242137-15-0 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-((2-carboxypropan-2-yl)amino)-2-fluorobenzoic acid; 4-isothiocyanato 2-(trifluoromethyl)benzonitrile With triethylamine In ethanol at 20℃; for 240h; Stage #2: With hydrogenchloride In ethanol; water 10 4-(l-Carboxy-l-methyl-ethylamino)-2-fluoro-benzoic acid (241 mg, 1 mmol), 4- isothiocyanato-2-trifluoromethylbenzonitrile (342 mg, 1.5 mmol) and triethylamine (343 mg, 3.4 mmol) were mixed in EtOH (5 mL) and the solution was stirred for 10 days at room temperature. The reaction mixture was concentrated under reduced pressure, the residue was acidified with 1M aqueous HC1, and the product was extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product obtained was purified by column chromatography eluting with ethyl acetate to obtain 4-[3-(4-cyano-3-trifluoromethyl-phenyl)-5,5-dimethyl-4- oxo-2-thioxo-imidazolidin-l-yl] -2-fluoro-benzoic acid (10 mg) as an off white solid.
With triethylamine In ethanol at 20℃; for 240h; Synthesis of 4-[3-(4-Cyano-3-trifluoromethyl-phenyl)-5,5-dimethyl-4-oxo-2-thioxo-imidazolidin-1-yl]-2-fluoro-benzoic acid (19) General procedure: Bromo compound 17 (27.5 g, 100 mmol), 4-isothiocyanato-2-trifluoromethylbenzonitrile 15 (34.2 g, 150 mmol) and triethylamine (34.3 g, 340 mmol) were mixed in EtOH (250 mL) and the solution was stirred for 10 days at room temperature. The reaction mixture was concentrated under reduced pressure, the residue was acidified with 1M aqueous HCl, and the product was extracted with ethyl acetate (250 mLx2). The combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product obtained was purified by column chromatography to obtain the desired product 19 (11.2 g, 23%yield).LCMS:
With triethylamine In ethanol at 80℃; 36.2 Step 2: Synthesis of intermediate WX036-5 Intermediate WX036-3 (0.1 g, 414.57 µmol) and compound WX036-4 (141.90 mg, 621.85 µmol) were added to ethanol (2 mL), and triethylamine (142.63 mg, 1.41 mmol, 196.19 µL) was slowly added to the reaction mixture. The mixture was stirred at 80 °C for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature, and rotary-evaporated to dryness under reduced pressure to remove the solvent. 20 mL of water was added, and the mixture was adjusted to pH of 3-4 with 1 M hydrochloric acid. The mixture was extracted with ethyl acetate (20 mL x 2), washed with saturated brine (20 mL x 2), dried over anhydrous sodium sulfate, and filtered. The filtrate was rotary-evaporated to dryness. The crude product was purified by column chromatography (eluent: dichloromethane:methanol = 1:0-10:1, v/v) to give the title compound WX036-5. (0481) MS-ESI m/z: 452.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6) δ: 10.04 (s, 1H), 8.41 (d, J = 8.3 Hz, 1H), 8.30 (d, J = 1.3 Hz, 1H), 8.11 - 8.05 (m, 2H), 7.47 (dd, J = 1.6, 11.2 Hz, 1H), 7.38 (dd, J = 1.8, 8.3 Hz, 1H), 1.56 (s, 6H).
With triethylamine In ethanol at 80℃; 36.2 Step 2: Synthesis of intermediate WX036-5 Intermediate WX036-3 (0.1 g, 414.57 µmol) and compound WX036-4 (141.90 mg, 621.85 µmol) were added to ethanol (2 mL), and triethylamine (142.63 mg, 1.41 mmol, 196.19 µL) was slowly added to the reaction mixture. The mixture was stirred at 80 °C for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature, and rotary-evaporated to dryness under reduced pressure to remove the solvent. 20 mL of water was added, and the mixture was adjusted to pH of 3-4 with 1 M hydrochloric acid. The mixture was extracted with ethyl acetate (20 mL x 2), washed with saturated brine (20 mL x 2), dried over anhydrous sodium sulfate, and filtered. The filtrate was rotary-evaporated to dryness. The crude product was purified by column chromatography (eluent: dichloromethane:methanol = 1:0-10:1, v/v) to give the title compound WX036-5. (0481) MS-ESI m/z: 452.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6) δ: 10.04 (s, 1H), 8.41 (d, J = 8.3 Hz, 1H), 8.30 (d, J = 1.3 Hz, 1H), 8.11 - 8.05 (m, 2H), 7.47 (dd, J = 1.6, 11.2 Hz, 1H), 7.38 (dd, J = 1.8, 8.3 Hz, 1H), 1.56 (s, 6H).

  • 3
  • [ 1289942-55-7 ]
  • [ 1242137-15-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 6 h / 100 °C / a sealed-tube 2: hydrogenchloride / water / 48 h / 120 °C
  • 4
  • [ 1242137-15-0 ]
  • [ 17994-94-4 ]
  • [ 2117637-78-0 ]
YieldReaction ConditionsOperation in experiment
47% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere; Methyl 7-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorobenzamido)heptanoate 7( 3-52). A flask was charged with compound 17 (130 mg, 0.29 mmol), methyl 7-aminoheptanoate hydrochloride (86 mg, 0.44 mmol) and HBTU (167 mg, 0.44 mmol), then filled with argon, DMF (3 mL) and DIPEA (0.15 mL, 0.87 mmol)) were added via syringe. The reaction mixture was stirred overnight at room temperature and quenched by adding water. Product was extracted with EtOAc and washed with water and brine, dried over Na2SO4. Purification by silica gel column (Hexane/EtOAc=2/1) provided the title compound (80 mg, 47%) as yellow oil. 1H NMR (600MHz, CDCl3): 8.24 (t, J=8.4Hz, 1H), 7.97 (d, J=8.4Hz, 1H), 7.94-7.92 (m, 1H), 7.81 (dd, J=8.4Hz, 1.8Hz, 1H), 7.22 (dd, J=8.4Hz, 1.8Hz, 1H), 7.13 (dd,J=11.4Hz, 1.8Hz, 1H), 6.71-6.66 (m, 1H), 3.65 (s, 3H), 3.51-3.45 (m, 2H), 2.30 (t, J=7.8Hz, 2H), 1.67-1.61 (m, 4H), 1.60 (s, 6H), 1.43-1.33 (m, 4H). 13C NMR (150MHz, CDCl3): 179.72, 174.42, 174.14, 161.95, 160.34 (d, J=248Hz), 138.90 (d, J=10.8Hz), 136.78, 135.29, 133.66 (q, J=33.3Hz), 133.38 (d, J=3.4Hz), 132.11, 127.04 (q, J=4.5Hz), 126.15 (d, J=3.0Hz), 122.90 (d, J=12.1Hz), 121.79 (q, J=273Hz), 117.89 (d, J=26.1Hz), 114.69, 110.39, 66.60, 51.50, 40.09, 33.91, 29.23, 28.70, 26.54, 24.75, 23.82. HR-ESI-MS m/z Calcd for C28H29F4N4O4S [M+H]+ 593.1846, found 593.1829.
47% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere; 1 Example 1. Methyl-7-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorobenzamido)heptanoate 7(3-52). A flask was charged with compound 17 (130 mg, 0.29 mmol), methyl 7-aminoheptanoate hydrochloride (86 mg, 0.44 mmol) and HBTU (167 mg, 0.44 mmol), then filled with argon, DMF (3 mL) and DIPEA (0.15 mL, 0.87 mmol)) were added via syringe. The reaction mixture was stirred overnight at room temperature and quenched by adding water. Product was extracted with EtOAc, washed with water and brine, and dried over Na2SO4. Purification by silica gel column (Hexane/EtOAc=2/1) provided the title compound (80 mg, 47%) as yellow oil. 1H NMR (600 MHz, CDCl3): δ 8.24 (t, J=8.4 Hz, 1H), 7.97 (d, J=8.4 Hz, 1H), 7.94-7.92 (m, 1H), 7.81 (dd, J=8.4 Hz, 1.8 Hz, 1H), 7.22 (dd, J=8.4 Hz, 1.8 Hz, 1H), 7.13 (dd, J=11.4 Hz, 1.8 Hz, 1H), 6.71-6.66 (m, 1H), 3.65 (s, 3H), 3.51-3.45 (m, 2H), 2.30 (t, J=7.8 Hz, 2H), 1.67-1.61 (m, 4H), 1.60 (s, 6H), 1.43-1.33 (m, 4H). 13C NMR (150 MHz, CDCl3): δ 179.72, 174.42, 174.14, 161.95, 160.34 (d, J=248 Hz), 138.90 (d, J=10.8 Hz), 136.78, 135.29, 133.66 (q, J=33.3 Hz), 133.38 (d, J=3.4 Hz), 132.11, 127.04 (q, J=4.5 Hz), 126.15 (d, J=3.0 Hz), 122.90 (d, J=12.1 Hz), 121.79 (q, J=273 Hz), 117.89 (d, J=26.1 Hz), 114.69, 110.39, 66.60, 51.50, 40.09, 33.91, 29.23, 28.70, 26.54, 24.75, 23.82. HR-ESI-MS m/z Calcd for C28H29F4N4O4S [M+H]+ 593.1846. found 593.1829.
  • 5
  • [ 1802242-47-2 ]
  • [ 1242137-15-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: dimethyl sulfoxide; Isopropyl acetate / 24 h / 95 °C / Large scale 2: sodium hydroxide / water; methanol / 4 h / 20 °C
Multi-step reaction with 2 steps 1: dimethyl sulfoxide; ethyl acetate / 18 h / 85 °C 2: sodium hydroxide / methanol / 4 h / 20 °C
Multi-step reaction with 2 steps 1: dimethyl sulfoxide; Isopropyl acetate / 40 h / 83 °C / Inert atmosphere; Large scale 2: lithium hydroxide monohydrate; water / tetrahydrofuran / 1 h / 40 °C / Large scale
Multi-step reaction with 2 steps 1: dimethyl sulfoxide; Isopropyl acetate / 60 h / 95 °C / Inert atmosphere 2: methanol; sodium hydroxide / tetrahydrofuran / 2 h / 40 °C
Multi-step reaction with 2 steps 1: dimethyl sulfoxide; Isopropyl acetate / 20 h / 90 °C 2: sodium hydroxide; water / tetrahydrofuran / 20 °C
Multi-step reaction with 2 steps 1: 90 °C 2: lithium hydroxide; water / tetrahydrofuran; methanol / 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: dimethyl sulfoxide; Isopropyl acetate / 20 h / 90 °C 2: sodium hydroxide / tetrahydrofuran / 20 °C
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / 20 h / 90 °C 2: lithium hydroxide; water / tetrahydrofuran; methanol / 5 h / 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: dimethyl sulfoxide; Isopropyl acetate / 60 h / 95 °C / Inert atmosphere 2: water; sodium hydroxide / tetrahydrofuran / 2 h / 40 °C
Multi-step reaction with 2 steps 1: tetrahydrofuran / 1 h / 0 °C / Inert atmosphere; Cooling with ice 2: lithium hydroxide / methanol; tetrahydrofuran; water / 4 h / 20 °C

  • 6
  • [ 1242137-15-0 ]
  • [ 510754-90-2 ]
  • [ 2308497-05-2 ]
YieldReaction ConditionsOperation in experiment
90% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h;
90% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h; 3 DIPEA (5 eq.) and HATU (1.2 eq.) were added to a solution of compound 50 (0426) (45.1 mg, 0.1 mmol) and /er/-butyl-(9-aminononyl)carbamate (1.1 eq.) in DMF (2 mL). After 30 min at rt, the mixture was subject to HPLC purification to afford Boc protected compound 54 with 90% yield. Then, compound 54 was obtained by a deprotection reaction in TFA/DCM solvent.
  • 7
  • [ 1242137-15-0 ]
  • [ 134857-22-0 ]
  • C33H38F4N4O4S [ No CAS ]
  • 8
  • [ 1242137-15-0 ]
  • [ 2287340-50-3 ]
  • [ 2308507-84-6 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h;
  • 9
  • [ 220851-29-6 ]
  • [ 1242137-15-0 ]
  • [ 2308497-65-4 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h;
  • 10
  • [ 1242137-15-0 ]
  • [ 245048-08-2 ]
  • [ 2308507-32-4 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h;
 

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