Pentylamine → 5-(2-Methoxy-4-pentylaminomethylphenoxy)pyrazine-2-carboxamide

HRID 130976Notes

Reaction equation

HRID 130976 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][CH2:23][CH2:24][CH3:25].[BH4-].[Na+]>CO>[CH3:20][O:19][C:5]1[CH:4]=[C:3]([CH2:1][NH:26][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[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 8060PentylamineHCID 4311764Sodium borohydrideHCID 597299775-(4-Formyl-2-methoxyphenoxy)pyrazine-2-carboxamide

Product 1

HCID 597302655-(2-Methoxy-4-pentylaminomethylphenoxy)pyrazine-2-carboxamideYield 71.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(4-formyl-2-methoxyphenoxy)pyrazine-2-carboxamide (Example 719, Part A) (0.200 g, 0.732 mmol), amylamine (0.0670 g, 0.769 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (3.6 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 60% to 90% (5% (2.0 M NH3 in methanol) in ethyl acetate) in hexanes. Concentrate the fractions containing the product. Take the solid up in ethyl acetate (50 mL) and wash with 1.0 N NaOH to give the title compound (0.180 g, 71.7%): TOF MS ES+ 345.2 (M+H)+, HRMS calcd for C18H25N4O3 345.1927 (M+H)+, found 345.1926, time 0.52 min; HPLC [Waters XTerra™ 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 23 min], tR=10.4 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 60% to 90% (5% (2.0 M NH3 in methanol) in ethyl acetate) in hexanes
  4. concentrationConcentrate the fractions
  5. additioncontaining the product
  6. washwash with 1.0 N NaOH

Sources & evidence

ORD record
ord-ddd4d48688214789948002359a596d43
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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