5-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-indole → tert-butyl (1-(4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamate

HRID 1529418Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529418
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([S:18]([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:13]=[C:12]2I.[CH3:29][O:30][C:31]1[CH:36]=[C:35]([Sn](C)(C)C)[N:34]=[C:33]([N:41]2[CH2:46][CH2:45][CH:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[CH2:43][CH2:42]2)[N:32]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([S:18]([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:13]=[C:12]2[C:35]1[CH:36]=[C:31]([O:30][CH3:29])[N:32]=[C:33]([N:41]2[CH2:46][CH2:45][CH:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:52])([CH3:51])[CH3:53])[CH2:43][CH2:42]2)[N:34]=1

Komponenten

6

Edukt 2

HCID 679602665-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-indoleHCID 86709790Tert-butyl (1-(4-methoxy-6-(trimethylstannyl)pyrimidin-2-yl)piperidin-4-yl)carbamate

Produkt 1

HCID 86709789tert-butyl (1-(4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamateAusbeute 43,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of 5-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-indole (0.107 g, 0.2 mmol) and tert-butyl (1-(4-methoxy-6-(trimethylstannyl)pyrimidin-2-yl)piperidin-4-yl)carbamate (0.1 g, 0.2 mmol) in DMF (2 mL) was added Pd(PPh3)4 (23 mg, 0.02 mmol) and CuI (42 mg, 0.22 mmol) and argon gas was bubbled for 15 min. The reaction was heated at 90° C. for 1 h then quenched with water. The suspension was extracted with EtOAc and the organic layer was dried (Na2SO4), filtered and concentrated. The residue was purified with basic alumina chromatography (eluting with 50% EtOAc in petroleum ether) to give tert-butyl (1-(4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamate (60 mg, 41%). MS (ESI, pos. ion) m/z: 690.2 (M+1); 1H-NMR (DMSO-d6, 300 MHz): δ ppm 8.71 (s, 1H), 8.61 (s, 1H), 8.10-8.20 (m, 3H), 7.42-7.52 (m, 4H), 7.20-7.25 (m, 3H), 6.76 (m, 1H), 4.56 (d, J=12.9 Hz, 2H), 3.87 (s, 3H), 3.32 (d, J=9 Hz, 3H), 3.03 (m, 2H) 2.33 (s, 3H), 1.74 (d, J=12.9 Hz, 2H), 1.3 (s, 9H).

Aufarbeitung

  1. customwas bubbled for 15 min
  2. customthen quenched with water
  3. extractionThe suspension was extracted with EtOAc
  4. dry with materialthe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified with basic alumina chromatography (eluting with 50% EtOAc in petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-9ab187c6562a42b4a705f2afaec88881
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

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