Diisopropylethylamine → (E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)-N-((tetrahydro-2H-pyran-2-yl)oxy)acrylamide

HRID 332865Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 332865
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:10]=3[C:9]=2[O:19][C:20]2[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28](O)=[O:29])=[CH:22][CH:21]=2)=[C:4]([CH3:31])[CH:3]=1.[O:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]1[O:38][NH2:39].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:10]=3[C:9]=2[O:19][C:20]2[CH:21]=[CH:22][C:23](/[CH:26]=[CH:27]/[C:28]([NH:39][O:38][CH:33]3[CH2:34][CH2:35][CH2:36][CH2:37][O:32]3)=[O:29])=[CH:24][CH:25]=2)=[C:4]([CH3:31])[CH:3]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86730646(E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

Produkt 1

HCID 86730650(E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)-N-((tetrahydro-2H-pyran-2-yl)oxy)acrylamideAusbeute 86,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a 30 mL screw cap vial, (E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (50 mg, 0.115 mmol) was dissolved in DMF (2 mL). The vial was charged with O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (27.0 mg, 0.230 mmol), HATU (65.6 mg, 0.173 mmol), and DIEA (0.060 mL, 0.345 mmol). The reaction mixture was stirred for 30 min at room temperature. The reaction was quenched with sat. NH4Cl and diluted with DCM. The organic phase was collected (phase separator) and concentrated by vacuum to afford to crude product. The crude material was purified by column chromatography (SiO2, 1-80% Heptanes/EtOAc) to afford (E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)-N-((tetrahydro-2H-pyran-2-yl)oxy)acrylamide (53 mg, 0.099 mmol, 86% yield). 1H NMR (400 MHz, CD3OD) δ ppm=1.48-1.73 (m, 3H), 1.73-1.96 (m, 3H), 2.36 (s, 3H), 3.56-3.70 (m, 1H), 3.89 (s, 3H), 3.98-4.14 (m, 1H), 4.96 (br. s., 1H), 6.35 (d, J=15.66 Hz, 1H), 6.79-6.95 (m, 3H), 6.95-7.07 (m, 2H), 7.26-7.39 (m, 2H), 7.39-7.48 (m, 3H), 7.52 (d, J=16.17 Hz, 1H). LC/MS (m/z, MH+): 534.1.

Aufarbeitung

  1. customTo a 30 mL screw cap vial
  2. customThe reaction was quenched with sat. NH4Cl
  3. additiondiluted with DCM
  4. customThe organic phase was collected (phase separator)
  5. concentrationconcentrated by vacuum
  6. customto afford to crude product
  7. customThe crude material was purified by column chromatography (SiO2, 1-80% Heptanes/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-847b077aad5c4b2f9ba48d590ac3ed0e
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08877801B2

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