Potassium Phosphate, Tribasic → 1-(4'-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid methyl ester

HRID 631916Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 631916
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH:9]([O:11][C:12](=[O:27])[NH:13][C:14]2[N:15]([CH3:26])[N:16]=[N:17][C:18]=2[C:19]2[CH:24]=[CH:23][C:22](Br)=[CH:21][CH:20]=2)[CH3:10])[CH:6]=[CH:7][CH:8]=1.CC1(C)C(C)(C)OB([C:38]2[CH:43]=[CH:42][C:41]([C:44]3([C:47]([O:49][CH3:50])=[O:48])[CH2:46][CH2:45]3)=[CH:40][CH:39]=2)O1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:50][O:49][C:47]([C:44]1([C:41]2[CH:42]=[CH:43][C:38]([C:22]3[CH:23]=[CH:24][C:19]([C:18]4[N:17]=[N:16][N:15]([CH3:26])[C:14]=4[NH:13][C:12]([O:11][CH:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:29])([F:28])[F:1])[CH:4]=4)[CH3:10])=[O:27])=[CH:20][CH:21]=3)=[CH:39][CH:40]=2)[CH2:46][CH2:45]1)=[O:48]

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 71264507Methyl 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropane-1-carboxylateHCID 118062436[5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid 1-(3-trifluoromethyl-phenyl)-ethyl ester

Produkt 1

HCID 1180627761-(4'-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid methyl esterAusbeute 53,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

[5-(4-Bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid 1-(3-trifluoromethyl-phenyl)-ethyl ester (680 mg, 1.45 mmol), methyl 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylate (525 mg, 1.74 mmol), X-Phos (138 mg, 0.29 mmol), palladium acetate (33 mg, 0.14 mmol) and potassium phosphate tribasic (923 mg, 4.35 mmol) were mixed in toluene (10 mL). Degassed water (2 mL) was added and the mixture was degassed with argon and then sealed. The mixture was stirred at 95° C. for 5 hrs until all starting material was consumed. The mixture was extracted with ethyl acetate and water. The organic layer was washed with brine and dried. Solvents were evaporated and the residue was purified by flash column chromatography (ethyl acetate in hexanes 5% to 70% in 15 minutes, 40 g silica gel) to give an amorphous white fluffy material as 1-(4′-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid methyl ester (436 mg, 53.3% yield). LC/MS calcd for C30H27F3N4O4 (m/e) 564.0, obsd 565.0 (M+H); 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.18-1.35 (m, 2.6H), 1.48-1.55 (m, 2H), 1.60 (br d, J=3.8 Hz, 2.4H), 3.57 (s, 3H), 3.86 (s, 3H), 5.80-5.90 (br m, 1H), 7.44 (d, J=8.3 Hz, 2.5H), 7.63 (d, J=8.1 Hz, 2.5H), 7.69 (br d, J=7.3 Hz, 3.5H), 7.80 (d, J=7.3 Hz, 3.5H), 9.65 and 10.06 (br s, 1H).

Aufarbeitung

  1. customthe mixture was degassed with argon
  2. customsealed
  3. customwas consumed
  4. extractionThe mixture was extracted with ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. customdried
  7. customSolvents were evaporated
  8. customthe residue was purified by flash column chromatography (ethyl acetate in hexanes 5% to 70% in 15 minutes, 40 g silica gel)

Quellen und Nachweise

ORD-Eintrag
ord-c585224eb85a41e5afba39abf2a14b7c
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321738B2

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