4-(1-Piperidylmethyl)phenylboronic Acid → tert-Butyl-{3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-carbamate

HRID 1888571Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1888571
[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[N:16]=[CH:15][C:14]2[NH:13][C:12]3[N:17]=[CH:18][C:19](Br)=[CH:20][C:11]=3[C:10]=2[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([CH2:29][C:30]2[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl.O>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[N:16]=[CH:15][C:14]2[NH:13][C:12]3[N:17]=[CH:18][C:19]([C:33]4[CH:32]=[CH:31][C:30]([CH2:29][N:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)=[CH:35][CH:34]=4)=[CH:20][C:11]=3[C:10]=2[CH:9]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 2

HCID 230053434-(1-Piperidylmethyl)phenylboronic AcidHCID 68346934tert-butyl-{3-Bromo-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-carbamate

Produkt 1

HCID 68346928tert-Butyl-{3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-carbamateAusbeute 30,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 10796Cesium carbonateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A degassed mixture of tert-butyl-{3-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-yl}-carbamate (229 mg, 0.631 mmol), 4-piperidin-1-ylmethyl-phenyl boronic acid (207 mg, 0.946 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (51.5 mg, 6.31 μmol, 10.0 mol %) in 1,4-dioxane (12.4 mL) and 2M aqueous cesium carbonate (1.32 mL) was heated under reflux for 5 h. The mixture was allowed to cool to room temperature, diluted with DCM and water, and filtered to remove the precipitate. The filtrate layers were separated and the aqueous phase was extracted with DCM, and the combined organic phase concentrated in vacuo. The resultant residue was dissolved in 20% methanol in DCM and absorbed onto silica gel for purification by flash chromatography (silica, 11 g column, Biotage, 1-20% methanol in DCM) to afford the title compound as a beige solid (86.9 mg, 30%). 1H NMR (DMSO-D6, 400 MHz): 11.96 (s, 1H), 9.55 (s, 1H), 8.99 (d, J=1.9 Hz, 1H), 8.88 (d, J=2.2 Hz, 1H), 8.57 (d, J=7.8 Hz, 2H), 7.80 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 3.50 (s, 2H), 2.35 (m, 4H), 1.55-1.45 (m, 4H), 1.52 (s, 9H), 1.39 (m, 2H). LCMS (Method D): RT=9.11 min, M+H+=458.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureunder reflux for 5 h
  3. filtrationfiltered
  4. customto remove the precipitate
  5. customThe filtrate layers were separated
  6. extractionthe aqueous phase was extracted with DCM
  7. concentrationthe combined organic phase concentrated in vacuo
  8. dissolutionThe resultant residue was dissolved in 20% methanol in DCM
  9. customabsorbed onto silica gel for purification by flash chromatography (silica, 11 g column, Biotage, 1-20% methanol in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-540ccd2374284ed99b975454979d52f2
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08501765B2

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