p-Fluorophenethylamine → 5-(4-{[2-(4-Fluorophenyl)ethylamino]methyl}-2-methylphenoxy)pyrazine-2-carboxamide

HRID 131004Notes

Reaction equation

HRID 131004 reaction equation
[CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[N:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=2)=[C:5]([CH3:19])[CH:4]=1)=O.[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][NH2:29])=[CH:23][CH:22]=1.[BH4-].[Na+]>CO>[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][NH:29][CH2:1][C:3]2[CH:18]=[CH:17][C:6]([O:7][C:8]3[N:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=3)=[C:5]([CH3:19])[CH:4]=2)=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 4653p-FluorophenethylamineHCID 4311764Sodium borohydrideHCID 597300545-(4-Formyl-2-methylphenoxy)pyrazine-2-carboxamide

Product 1

HCID 597303205-(4-{[2-(4-Fluorophenyl)ethylamino]methyl}-2-methylphenoxy)pyrazine-2-carboxamideYield 54%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(4-formyl-2-methylphenoxy)pyrazine-2-carboxamide (Example 404, part D) (0.600 g, 2.33 mmol), 2-(4-fluorophenyl)ethylamine (0.325 g, 2.33 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (11.7 mL), cap and stir overnight. Add NaBH4 (0.088 g, 2.33 mmol) 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 5% to 20% (2.0 M NH3 in methanol) in ethyl acetate. Concentrate the fraction containing the product, then take it up in EtOAc (100 mL). Wash the organic solution with 1.0 N NaOH (2×25 mL), dry it over Na2SO4 and concentrate it to give the title compound (0.478 g, 54.0%): TOF MS ES+ 381.2 (M+H)+, HRMS calcd for C21H22N4O2F 381.1727 (M+H)+, found 381.1729, time 0.39 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=11.3 min, 97.8% 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 5% to 20% (2.0 M NH3 in methanol) in ethyl acetate
  4. concentrationConcentrate the fraction
  5. additioncontaining the product
  6. washWash the organic solution with 1.0 N NaOH (2×25 mL)
  7. dry with materialdry it over Na2SO4
  8. concentrationconcentrate it

Sources & evidence

ORD record
ord-ec8f1ca432fc4522bbd7b395d051e32a
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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