Cesium fluoride → 5'-Ethenyl-1'-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618769Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1618769
Br[C:2]1[N:7]=[C:6]2[C:8]3([CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH2:9][N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:12]=3[CH3:28])[C:5]2=[CH:4][C:3]=1[N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.[F-].[Cs+].[CH2:42]([Sn](CCCC)(CCCC)C=C)[CH2:43]CC>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:42]([C:2]1[N:7]=[C:6]2[C:8]3([CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[CH2:9][N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:12]=3[CH3:28])[C:5]2=[CH:4][C:3]=1[N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1)=[CH2:43]

Komponenten

6

Edukt 3

HCID 25953Cesium fluorideHCID 81998TributylvinyltinHCID 866642805'-Bromo-1'-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Produkt 1

HCID 672849095'-Ethenyl-1'-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418851HCID 178418851, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a stirred solution of 5′-bromo-1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (140 mg, 0.237 mmol) in 1,4-dioxane (4 mL) was added bis(tri-tert-butylphosphine)palladium (0) (12.12 mg, 0.024 mmol), cesium fluoride (36 mg, 0.237 mmol) and tri-n-butyl(vinyl)tin (90 μL, 0.285 mmol) and the reaction was heated at 120° C. for 3 h in the microwave. After this time the reaction was partitioned between EtOAc (50 mL) and water (15 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. The crude reaction was purified by column chromatography on silica gel (DCM to DCM:MeOH:—NH4OH (9:1:0.4), 1:0 to 2:1 as eluent) to give 5′-ethenyl-1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]. 1H NMR (400 MHz, chloroform-d) δ ppm 8.66-8.80 (1H, m), 7.85-7.96 (3H, m), 7.73 (1H, dd, J=9.3, 6.0 Hz), 7.42 (1H, ddd, J=6.8, 4.8, 2.1 Hz), 7.23-7.30 (1H, m), 7.09 (1H, dd, J=17.2, 10.8 Hz), 6.30 (1H, dd, J=17.3, 2.6 Hz), 5.96 (1H, s), 5.18-5.36 (1H, m), 4.23-4.32 (2H, m), 3.93-4.03 (2H, m), 3.77 (4H, t, J=4.6 Hz), 3.61-3.69 (2H, m), 2.68-2.80 (4H, m), 2.27-2.47 (5H, m), 1.77-1.90 (2H, m). Mass Spectrum (ESI) m/e=538.2 (M+1).

Aufarbeitung

  1. customAfter this time the reaction was partitioned between EtOAc (50 mL) and water (15 mL)
  2. dry with materialThe separated organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe crude reaction
  6. customwas purified by column chromatography on silica gel (DCM to DCM:MeOH:—NH4OH (9:1:0.4), 1:0 to 2:1 as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-a377bc5fce4a4b99a543dfce84f70cf2
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765940B2

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