Isoamylamine → 5-{2-Methoxy-4-[(3-methylbutylamino)methyl]phenoxy}pyrazine-2-carboxamide

HRID 492616Notes

Reaction equation

HRID 492616 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]([O:19][CH3:20])[CH:4]=1)=O.[CH2:21]([NH2:26])[CH2:22][CH:23]([CH3:25])[CH3:24].[BH4-].[Na+]>CO>[CH3:20][O:19][C:5]1[CH:4]=[C:3]([CH2:1][NH:26][CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])[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 7894IsoamylamineHCID 4311764Sodium borohydrideHCID 597299775-(4-Formyl-2-methoxyphenoxy)pyrazine-2-carboxamide

Product 1

HCID 117250605-{2-Methoxy-4-[(3-methylbutylamino)methyl]phenoxy}pyrazine-2-carboxamideYield 54.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(4-formyl-2-methoxyphenoxy)pyrazine-2-carboxamide (Example 719, Part A) (0.700 g, 2.56 mmol), isoamylamine (0.234 g, 2.69 mmol) and 3 Å molecular sieves in a vial. Add methanol (12.8 mL), cap and stir overnight. Add NaBH4 (0.0969 g, 2.56 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 over 45 minutes. Concentrate the fraction containing the product, and dissolve it in EtOAc (100 mL). Wash the organic solution with 1.0 N NaOH (2× 25 mL), dry it over Na2SO4, filter and concentrate to give the title compound (0.484 g, 54.9%): TOF MS ES+ 345.2 (M+H)+, HRMS calcd for C18H25N4O3 345.1927 (M+H)+, found 345.1938, time 0.38 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=10.1 min, 95.4% 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 over 45 minutes
  4. concentrationConcentrate the fraction
  5. additioncontaining the product
  6. dissolutiondissolve it in EtOAc (100 mL)
  7. washWash the organic solution with 1.0 N NaOH (2× 25 mL)
  8. dry with materialdry it over Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-a6300e729c534ac49fc2c8e47890d91e
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

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