Toluene → ethyl [(1S)-5-(2-{2-[4'-(5-acetyl-2-thienyl)-1,1'-biphenyl-4-yl]-5-methyl-1,3-oxazol-4-yl}ethoxy)-2,3-dihydro-1H-inden-1-yl]acetate

HRID 1040274Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1040274
[CH2:1]([O:3][C:4](=[O:31])[CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH2:16][CH2:17][C:18]3[N:19]=[C:20]([C:24]4[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=4)[O:21][C:22]=3[CH3:23])=[CH:12][CH:13]=2)[CH2:8][CH2:7]1)[CH3:2].[C:32]([C:35]1[S:39][C:38](B(O)O)=[CH:37][CH:36]=1)(=[O:34])[CH3:33].C(=O)([O-])[O-].[Na+].[Na+].[C:49]1(C)[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>O1CCOCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[CH2:1]([O:3][C:4](=[O:31])[CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH2:16][CH2:17][C:18]3[N:19]=[C:20]([C:24]4[CH:29]=[CH:28][C:27]([C:49]5[CH:54]=[CH:53][C:52]([C:38]6[S:39][C:35]([C:32](=[O:34])[CH3:33])=[CH:36][CH:37]=6)=[CH:51][CH:50]=5)=[CH:26][CH:25]=4)[O:21][C:22]=3[CH3:23])=[CH:12][CH:13]=2)[CH2:8][CH2:7]1)[CH3:2]

Komponenten

8

Edukt 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 4143377(5-Acetylthiophen-2-yl)boronic acidHCID 69053646(1S)-(5-{2-[2-(4-bromo-phenyl)-5-methyl-oxazole-4-yl]-ethoxy}-indan-1-yl)-acetic acid ethyl ester

Produkt 1

HCID 86590243ethyl [(1S)-5-(2-{2-[4'-(5-acetyl-2-thienyl)-1,1'-biphenyl-4-yl]-5-methyl-1,3-oxazol-4-yl}ethoxy)-2,3-dihydro-1H-inden-1-yl]acetateAusbeute 46 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24290Palladium ChlorideKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a solution containing ethyl((1S)-5-{2-[2-(4-bromophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}-2,3-dihydro-1H-inden-1-yl)acetate (0.100 g, 0.21 mmol) [prepared from 2-[5-methyl-2-(4-bromophenyl)-1,3-oxazol-4-yl]ethanol and ethyl [(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate (Example 135)], 1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II) (16.9 mg, 0.02 mmol), and 5-acetyl-2-thienylboronic acid (0.062 g, 0.41 mmol) in degassed toluene and dioxane (4:1, 2 mL) was added aqueous 2 M sodium carbonate (0.5 mL). The mixture was heated at 85° C. for 16 hours. Solvents were evaporated under vacuum and the residue was dissolved in methanol and acetonitrile and filtered through a C8 reverse phase extraction cartridge. Solvents were evaporated and the residue was dissolved in acetonitrile and purified by HPLC to obtain ethyl[(1S)-5-(2-{2-[4′-(5-acetyl-2-thienyl)-1,1′-biphenyl-4-yl]-5-methyl-1,3-oxazol-4-yl}ethoxy)-2,3-dihydro-1H-inden-1-yl]acetate in 46% yield. (50 mg, 0.09 mmol) MS (electro spray) 530.4 (M+H)+, 1H NMR (CDCl3) δ 1.24 (t, 3H), 1.71 (m, 1H), 2.37 (m, 5H), 2.57 (s, 3H), 2.68 (m, 1H), 2.83 (m, 2H), 3.03 (m, 2H), 3.48 (m, 1H), 4.17(m, 4H), 6.67 (m, 2H), 7.02 (d, 1H), 7.39 (d, 1H), 7.67 (d, 1H), 7.73 (d, 2H), 8.01 (d, 2H).

Aufarbeitung

  1. customSolvents were evaporated under vacuum
  2. dissolutionthe residue was dissolved in methanol
  3. filtrationacetonitrile and filtered through a C8 reverse phase extraction cartridge
  4. customSolvents were evaporated
  5. dissolutionthe residue was dissolved in acetonitrile
  6. custompurified by HPLC

Quellen und Nachweise

ORD-Eintrag
ord-8defe28573824607ae8cd1549bb482d9
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08552203B2

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