Potassium Carbonate → (4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1-pyrimidin-5-yl-1H-indol-2-yl]-methanone

HRID 19875

Reaktionsgleichung

Reaktionsgleichung von HRID 19875
[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.Br[C:31]1[CH:32]=[N:33][CH:34]=[N:35][CH:36]=1.N[C@@H]1CCCC[C@H]1N.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.[Cu]I>[F:29][C:2]1([F:1])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[N:11]([C:31]3[CH:32]=[N:33][CH:34]=[N:35][CH:36]=3)[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]([CH3:27])[CH3:28])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1

Komponenten

8

Edukt 5

HCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 783445-BromopyrimidineHCID 11603838(4,4-Difluoropiperidin-1-yl)[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]methanone2×

Produkt 1

HCID 16739594(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1-pyrimidin-5-yl-1H-indol-2-yl]-methanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 312751,4-DioxaneLösungsmittel

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.), 5-bromopyrimidine (44 mg, 1.1 eq.), trans-1,2-diaminocyclohexane (18 mg, 0.65 eq.), copper(I) iodide (6 mg, 0.12 eq.) and potassium phosphate tribasic (110 mg, 2.1 eq.) in dioxan (2.0 mL) was stirred under reflux for 3 d. Potassium carbonate (72 mg, 2.1 eq.) was added and the mixture was refluxed for 1 d, evaporated to dryness and purified on silica gel, eluting with a 49:1:0 to 95:5:0.25 gradient of dichloromethane/methanol/ammonium hydroxide, to yield 121 mg (100%) from the desired product as orange oil. MS (m/e): 484.4 (MH+, 100%).

Aufarbeitung

  1. temperatureunder reflux for 3 d
  2. temperaturethe mixture was refluxed for 1 d
  3. customevaporated to dryness
  4. custompurified on silica gel
  5. washeluting with a 49:1:0 to 95:5:0.25 gradient of dichloromethane/methanol/ammonium hydroxide

Quellen und Nachweise

ORD-Eintrag
ord-04dbb6dd054b486abc4037184ed14b2a
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745479B2

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