2-(2,4-difluorophenyl)ethanamine → HCID 59730022, compound

HRID 130974Notes

Reaction equation

HRID 130974 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.[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[CH2:29][CH2:30][NH2:31].[BH4-].[Na+]>CO>[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[CH2:29][CH2:30][NH:31][CH2:1][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

Participants

5

Reactant 3

HCID 36892392-(2,4-difluorophenyl)ethanamineHCID 4311764Sodium borohydrideHCID 597300166-(4-Formyl-2-methoxyphenoxy)nicotinamide

Product 1

HCID 59730022HCID 59730022, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 6-(4-formyl-2-methoxyphenoxy)nicotinamide (Example 414, Part B) (0.300 g, 1.10 mmol), 2-(2,4-difluorophenyl)ethylamine (0.343 g, 2.184 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (4.4 mL), cap and stir overnight. Add NaBH4 (ca. 3-5 eq in two portions) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 2% to 20% (2.0 M NH3 in methanol) in ethyl acetate to give 6-(4-{[2-(2,4-difluorophenyl)ethylamino]methyl}-2-methoxyphenoxy)nicotinamide. Dissolve the compound in methanol (5.0 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: TOF MS ES+ 414.2 (M+H)+, HRMS calcd for C22H22N3O3F2 414.1629 (M+H)+, found 414.1613, time 0.52 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18 min], tR=11.6 min, 100% purity.

Workup

  1. customDry the column in a vacuum oven at room temperature
  2. customPurify
  3. washby eluting through a 40 g ISCO® column with 2% to 20% (2.0 M NH3 in methanol) in ethyl acetate

Sources & evidence

ORD record
ord-e12f44fe617f4ae380524ab32eb8f468
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

Loading…