Potassium Hydroxide → 6-(1-methyl-piperidin-4-yloxy)-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamide

HRID 1677108Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1677108
N1([C:7]2[CH:30]=[CH:29][C:10]([C:11]([NH:13][CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:18][CH:17]=3)=[O:12])=[CH:9][N:8]=2)CCOCC1.[OH:31][CH:32]1[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]1.[OH-].[K+]>CS(C)=O.C(Cl)Cl.O>[CH3:38][N:35]1[CH2:36][CH2:37][CH:32]([O:31][C:7]2[CH:30]=[CH:29][C:10]([C:11]([NH:13][CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:18][CH:17]=3)=[O:12])=[CH:9][N:8]=2)[CH2:33][CH2:34]1

Komponenten

7

Edukt 3

HCID 14797Potassium HydroxideHCID 660484-Piperidinol, 1-methyl-HCID 575716996-Morpholin-4-yl-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamide2×

Produkt 1

HCID 251820966-(1-methyl-piperidin-4-yloxy)-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamideAusbeute 20,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of 6-chloro-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamide (130 mg, intermediate from example 23) in DMSO (1.4 ml) was treated with 4-hydroxy-N-methylpiperidine (68 mg) and KOH (93 mg). The reaction mixture was heated for 20 min at 100° C. in the microwave oven. Then it was cooled to r.t. and diluted with CH2Cl2 and water. The aqueous layer was washed with CH2Cl2. The combined organic layers were dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 98:2) to give 6-(1-methyl-piperidin-4-yloxy)-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamide (29 mg) as off-white solid. MS (ISP): 432.2 ([M+H]+)

Aufarbeitung

  1. temperatureThen it was cooled to r.t.
  2. washThe aqueous layer was washed with CH2Cl2
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 98:2)

Quellen und Nachweise

ORD-Eintrag
ord-933d96172b544c4fa54e4ce18e58dd17
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08008305B2

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