2-(Pyridin-3-yl)ethan-1-amine → 5-{2-Methyl-4-[(2-pyridin-3-yl-ethylamino)methyl]phenoxy}pyrazine-2-carboxamide

HRID 131005Notes

Reaction equation

HRID 131005 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.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][CH2:27][NH2:28])[CH:21]=1.[BH4-].[Na+]>CO>[CH3:19][C:5]1[CH:4]=[C:3]([CH2:1][NH:28][CH2:27][CH2:26][C:22]2[CH:21]=[N:20][CH:25]=[CH:24][CH:23]=2)[CH:18]=[CH:17][C:6]=1[O:7][C:8]1[N:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=1

Participants

5

Reactant 3

HCID 8540512-(Pyridin-3-yl)ethan-1-amineHCID 4311764Sodium borohydrideHCID 597300545-(4-Formyl-2-methylphenoxy)pyrazine-2-carboxamide

Product 1

HCID 597303145-{2-Methyl-4-[(2-pyridin-3-yl-ethylamino)methyl]phenoxy}pyrazine-2-carboxamideYield 37.2%

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-pyridin-3-ylethylamine (0.285 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 25% (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 (0.315 g, 37.2%): TOF MS ES+ 364.2 (M+H)+, HRMS calcd for C20H22N5O2 364.1773 (M+H)+, found 367.1774, 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=6.1 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 5% to 25% (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-412bedb942724dd6930e9869624a7282
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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