5-chloro-3-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine → (5-Chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-fluoro-5-methoxy-4-(1-methyl-1H-benzoimidazol-2-ylmethoxy)-phenyl]-methanol

HRID 253462

Reaktionsgleichung

Reaktionsgleichung von HRID 253462
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[CH:9][N:8]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[C:5]2=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[F:27][C:28]1[CH:35]=[C:34]([O:36][CH2:37][C:38]2[N:42]([CH3:43])[C:41]3[CH:44]=[CH:45][CH:46]=[CH:47][C:40]=3[N:39]=2)[C:33]([O:48][CH3:49])=[CH:32][C:29]=1[CH:30]=[O:31]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:30]([C:29]3[CH:32]=[C:33]([O:48][CH3:49])[C:34]([O:36][CH2:37][C:38]4[N:42]([CH3:43])[C:41]5[CH:44]=[CH:45][CH:46]=[CH:47][C:40]=5[N:39]=4)=[CH:35][C:28]=3[F:27])[OH:31])=[CH:9][N:8]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[C:5]2=[N:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 580879285-chloro-3-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 598038732-fluoro-5-methoxy-4-(1-methyl-1H-benzimidazol-2-ylmethoxy)-benzaldehydeHCID 178418918HCID 178418918, Verbindung

Produkt 1

HCID 66888056(5-Chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-fluoro-5-methoxy-4-(1-methyl-1H-benzoimidazol-2-ylmethoxy)-phenyl]-methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
-25 °C

Versuchsvorschrift

5-Chloro-3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (144, 0.235 g, 0.541 mmol, prepared as described in Example 49) was dissolved in tetrahydrofuran (5 mL, 60 mmol). The solution was cooled to −25° C. After the addition of 2 M of isopropylmagnesium chloride in tetrahydrofuran (400 μL) the reaction was warmed to −10° C. with stirring. The reaction was cooled to −30° C. and 2-fluoro-5-methoxy-4-(1-methyl-1H-benzimidazol-2-ylmethoxy)-benzaldehyde (143, 0.170 g, 0.541 mmol) in 4 mL of tetrahydrofuran was added at once to the mixture. The reaction warmed to −10° C. and then evaporated to dryness. Ethyl acetate was added and the organic portion was washed with saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate and concentrated. Purification with silica gel flash chromatography with a gradient of ethyl acetate (5 to 80%) in hexanes gave the desired compound 145.

Aufarbeitung

  1. temperaturewas warmed to −10° C.
  2. temperatureThe reaction was cooled to −30° C.
  3. temperatureThe reaction warmed to −10° C.
  4. customevaporated to dryness
  5. additionEthyl acetate was added
  6. washthe organic portion was washed with saturated sodium bicarbonate solution and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customPurification with silica gel flash chromatography with a gradient of ethyl acetate (5 to 80%) in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-188f16f3a0b247b58f64d9b468716e79
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07872018B2

Verknüpfte Notizen

Wird geladen…