p-Methylphenethylamine → 6-{2-Methoxy-4-[(2-p-tolylethylamino)methyl]phenoxy}nicotinamide

HRID 130870

Reaktionsgleichung

Reaktionsgleichung von HRID 130870
[CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=2)=[C:5]([O:19][CH3:20])[CH:4]=1)=O.[C:21]1([CH3:30])[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][NH2:29])=[CH:23][CH:22]=1.[BH4-].[Na+]>CO>[CH3:20][O:19][C:5]1[CH:4]=[C:3]([CH2:1][NH:29][CH2:28][CH2:27][C:24]2[CH:25]=[CH:26][C:21]([CH3:30])=[CH:22][CH:23]=2)[CH:18]=[CH:17][C:6]=1[O:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=1

Komponenten

5

Edukt 3

HCID 76751p-MethylphenethylamineHCID 4311764Sodium borohydrideHCID 597300166-(4-Formyl-2-methoxyphenoxy)nicotinamide

Produkt 1

HCID 597303426-{2-Methoxy-4-[(2-p-tolylethylamino)methyl]phenoxy}nicotinamideAusbeute 99,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

Place 6-(4-formyl-2-methoxyphenoxy)nicotinamide (Example 414, Part B) (0.100 g, 0.367 mmol), 2-p-tolylethylamine (0.0546 g, 0.404 mmol) and 3 Å molecular sieves in a vial. Add methanol (3.6 mL), cap and stir overnight. Add NaBH4 (in excess over two portions) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 5 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 10 g ISCO® column with (2.0 M NH3 in methanol) in ethyl acetate to give 6-{2-methoxy-4-[(2-p-tolylethylamino)methyl]phenoxy}nicotinamide (0.143 g, 97.8%). Dissolve the compound in dichloromethane (2.5 mL) and add 1 equivalent of 0.50 M methanesulfonic acid in dichloromethane. Stir the solution for a short time before concentrating to give the title compound (0.168 g, ˜100%): TOF MS ES+ 392.1 (M+H)+, HRMS calcd for C23H26N3O3 392.1974 (M+H)+, found 392.1966, time 0.39 min; HPLC [Waters XTerra™ MS C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95% over 15 min], tR=8.4 min, 100% purity.

Aufarbeitung

  1. customDry the column in a vacuum oven at room temperature
  2. customPurify
  3. washby eluting through a 10 g ISCO® column with (2.0 M NH3 in methanol) in ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-e8a5faafa09d4ac5b68b3b7c49be2f6d
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07381719B2

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