(S)-(+)-3-Hydroxytetrahydrofuran → (S)-6-(2-Chloro-4-((tetrahydrofuran-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole

HRID 1487606Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1487606
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=2[N:7]=1.[O:30]1[CH2:34][CH2:33][C@H:32]([OH:35])[CH2:31]1.CC(C)([O-])C.[Na+]>O1CCOCC1>[Cl:1][C:2]1[N:3]=[C:4]([O:35][C@H:32]2[CH2:33][CH2:34][O:30][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:26])[CH3:27])[C:6]=2[N:7]=1

Komponenten

5

Edukt 3

HCID 2733227(S)-(+)-3-HydroxytetrahydrofuranHCID 23676156Sodium t-butoxideHCID 867264196-(2,4-Dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole

Produkt 1

HCID 86726440(S)-6-(2-Chloro-4-((tetrahydrofuran-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazoleAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

To a solution of 6-(2,4-dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole (1 equiv), (S)-tetrahydrofuran-3-ol (1.1 equiv) in 1,4-dioxane (0.2 M) was added sodium tert-butoxide (1.1 equiv). The reaction was stirred at 75° C. for 5 h. The reaction mixture was quenched with saturated aqueous sodium chloride and then washed with ethyl acetate. The organic phase was combined and washed with saturated aqueous sodium chloride. The organic layer was dried (magnesium sulfate), filtered, and concentrated. The crude was purified by silica gel column chromatography (0-90%) ethyl acetate in hexane) to give the title compound (90% yield) as yellow solid; 1H NMR (400 MHz, DMSO-d6) δ ppm −0.07 (s, 9H) 0.84-0.90 (m, 2H) 1.99-2.10 (m, 1H) 2.26 (dtd, J=13.96, 8.25, 8.25, 6.25 Hz, 1H) 2.63 (s, 3H) 3.53-3.62 (m, 2H) 3.73-3.81 (m, 2H) 3.84 (d, J=10.54 Hz, 1H) 3.93 (dd, J=10.54, 4.30 Hz, 1H) 5.57 (s, 2H) 5.72-5.80 (m, 1H) 7.59-7.64 (m, 1H) 7.66 (d, J=8.59 Hz, 1H) 7.89 (s, 1H) 7.91 (d, J=0.78 Hz, 1H); MS (ESI) m/z 501.1 [M+1]+.

Aufarbeitung

  1. customThe reaction mixture was quenched with saturated aqueous sodium chloride
  2. washwashed with ethyl acetate
  3. washwashed with saturated aqueous sodium chloride
  4. dry with materialThe organic layer was dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was purified by silica gel column chromatography (0-90%) ethyl acetate in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-58da91637f704ad8af7434860da175df
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09428509B2

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