Isohexylamine → 6-{2-Methoxy-4-[(4-methylpentylamino)methyl]phenoxy}nicotinamide

HRID 130869Notes

Reaction equation

HRID 130869 reaction equation
[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.[CH3:21][CH:22]([CH3:27])[CH2:23][CH2:24][CH2:25][NH2:26].[BH4-].[Na+]>CO>[CH3:20][O:19][C:5]1[CH:4]=[C:3]([CH2:1][NH:26][CH2:25][CH2:24][CH2:23][CH:22]([CH3:27])[CH3:21])[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

Participants

5

Reactant 3

HCID 219608IsohexylamineHCID 4311764Sodium borohydrideHCID 597300166-(4-Formyl-2-methoxyphenoxy)nicotinamide

Product 1

HCID 597301166-{2-Methoxy-4-[(4-methylpentylamino)methyl]phenoxy}nicotinamideYield 99.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 6-(4-formyl-2-methoxyphenoxy)nicotinamide (Example 414, Part B) (0.100 g, 0.367 mmol), 4-methylpentylamine (Part A, 0.0409 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-[(4-methylpentylamino)methyl]phenoxy}nicotinamide (0.131 g, 71.8%). Dissolve the compound in dichloromethane (2.5 mL) and add 1 equivalent of 0.50M methanesulfonic acid in dichloromethane. Stir the solution for a short time before concentrating to give the title compound (0.124 g, ˜100%): TOF MS ES+ 358.2 (M+H)+, HRMS calcd for C20H28N3O3 358.2131 (M+H)+, found 358.2119, 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=8.2 min, 100% purity.

Workup

  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

Sources & evidence

ORD record
ord-ee5bace7cf8947e6a7fa49e479c9a4f5
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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