Potassium Carbonate → 2-Methoxy-6-(6-methoxy-4-((4-phenylthiazol-2-yl)methoxy)benzofuran-2-yl)imidazo[2,1-b][1,3,4]thiadiazole

HRID 625096Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 625096
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[O:9][C:8]([C:10]3[N:11]=[C:12]4[N:16]([CH:17]=3)[N:15]=[C:14]([O:18][CH3:19])[S:13]4)=[CH:7][C:6]2=[C:20]([OH:22])[CH:21]=1.Br[CH2:24][C:25]1[S:26][CH:27]=[C:28]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:29]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:19][O:18][C:14]1[S:13][C:12]2=[N:11][C:10]([C:8]3[O:9][C:5]4[CH:4]=[C:3]([O:2][CH3:1])[CH:21]=[C:20]([O:22][CH2:24][C:25]5[S:26][CH:27]=[C:28]([C:30]6[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=6)[N:29]=5)[C:6]=4[CH:7]=3)=[CH:17][N:16]2[N:15]=1

Komponenten

5

Edukt 3

HCID 11430Potassium Carbonate2×HCID 534821022-(Bromomethyl)-4-phenyl-1,3-thiazoleHCID 722017096-Methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-ol

Produkt 1

HCID 721933292-Methoxy-6-(6-methoxy-4-((4-phenylthiazol-2-yl)methoxy)benzofuran-2-yl)imidazo[2,1-b][1,3,4]thiadiazoleAusbeute 94 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A suspension of 6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-ol (Example 1H, 0.080 g, 0.252 mmol) and 2-(bromomethyl)-4-phenylthiazole (0.128 g, 0.504 mmol) in N,N-Dimethylformamide (3 mL) was maintained under vacuum (10 mbar) for 5 minutes. The flask was then flushed with nitrogen and anhydrous freshly powdered (mortar and pestle) potassium carbonate (0.105 g, 0.756 mmol) was added all at once. The resulting mixture was stirred at room temperature with a few short sonication periods (˜1 min) for 1 hour. The heterogeneous mixture became almost homogeneous (except the potassium carbonate) after 10 min and started to precipitate again to a cream solid. The reaction mixture was quenched with 1N hydrochloric acid (2 mL) and then partitioned between dichloromethane (150 mL) and saturated sodium bicarbonate (20 mL). The organic phase was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The solid pale yellow residue was chromatographed on silica gel (2.5×6 cm, elution dichloromethane-ethyl acetate 0-2-5%) to give the title material (0.116 g, 94%) as a pale yellow solid. Crystallization in ethyl acetate (12 mL) provided the title material (0.086 g) as a pale yellow solid. LC (Method C): 2.474 min. HRMS (ESI) calcd for C24H9N4O4S2 [M+H]+ m/z 491.0842, found 491.0864. 1H NMR (CDCl3, 400 MHz) δ ppm: 3.86 (s, 3H), 4.22 (s, 3H), 5.54 (s, 2H), 6.48 (d, J=1.96 Hz, 1H), 6.75 (broad d, 1H), 7.15 (s, 1H), 7.32-7.39 (m, 1H), 7.41-7.49 (m, 2H), 7.53 (s, 1H), 7.87 (s, 1H), 7.90-7.95 (m, 2H).

Aufarbeitung

  1. temperaturewas maintained under vacuum (10 mbar) for 5 minutes
  2. customThe flask was then flushed with nitrogen
  3. additionwas added all at once
  4. customafter 10 min
  5. customto precipitate again to a cream solid
  6. customThe reaction mixture was quenched with 1N hydrochloric acid (2 mL)
  7. custompartitioned between dichloromethane (150 mL) and saturated sodium bicarbonate (20 mL)
  8. washThe organic phase was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe solid pale yellow residue was chromatographed on silica gel (2.5×6 cm, elution dichloromethane-ethyl acetate 0-2-5%)

Quellen und Nachweise

ORD-Eintrag
ord-4e7c7c9a138546ed8a2e36373155d5eb
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09303065B2

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