Pyridine → [1-(3,5-Difluoro-phenyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone

HRID 19847

Reaktionsgleichung

Reaktionsgleichung von HRID 19847
[F:1][C:2]1([F:29])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.[F:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[C:35]([F:37])[CH:36]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:30][C:31]1[CH:32]=[C:33]([N:11]2[C:12]3[C:17](=[CH:16][C:15]([O:19][CH:20]4[CH2:25][CH2:24][N:23]([CH:26]([CH3:27])[CH3:28])[CH2:22][CH2:21]4)=[CH:14][CH:13]=3)[CH:18]=[C:10]2[C:8]([N:5]2[CH2:6][CH2:7][C:2]([F:1])([F:29])[CH2:3][CH2:4]2)=[O:9])[CH:34]=[C:35]([F:37])[CH:36]=1

Komponenten

6

Edukt 3

HCID 1049PyridineHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 11603838(4,4-Difluoropiperidin-1-yl)[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]methanone2×

Produkt 1

HCID 16739413[1-(3,5-Difluoro-phenyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8895Cupric acetateKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (intermediate 1, 100 mg, 1.0 eq.), anhydrous copper(II) acetate (90 mg, 2.0 eq.), 3,5-difluorophenylboronic acid (123 mg, 3 eq.) and pyridine (80 uL, 4 eq.) in dichloromethane (2.5 mL) was stirred at room temperature for 2 days, evaporated to dryness and purified on silica gel, eluting with a 98:2 to 95:5 gradient of dichloromethane/methanol, to yield 79 mg (61%) from the desired product as light yellow foam. MS (m/e): 518.4 (MH+, 100%).

Aufarbeitung

  1. customevaporated to dryness
  2. custompurified on silica gel
  3. washeluting with a 98:2 to 95:5 gradient of dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-d70fcd0359ab47f8b28dc0012ec92a30
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745479B2

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