3,3-Dimethylbutylamine → 5-{4-[(3,3-Dimethylbutylamino)methyl]-2-methylphenoxy}pyrazine-2-carboxamide

HRID 228325Notes

Reaction equation

HRID 228325 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.[CH3:20][C:21]([CH3:26])([CH3:25])[CH2:22][CH2:23][NH2:24].[BH4-].[Na+]>CO>[CH3:20][C:21]([CH3:26])([CH3:25])[CH2:22][CH2:23][NH:24][CH2:1][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

Participants

5

Reactant 3

HCID 197093,3-DimethylbutylamineHCID 4311764Sodium borohydrideHCID 597300545-(4-Formyl-2-methylphenoxy)pyrazine-2-carboxamide

Product 1

HCID 597303555-{4-[(3,3-Dimethylbutylamino)methyl]-2-methylphenoxy}pyrazine-2-carboxamideYield 41.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(4-formyl-2-methylphenoxy)pyrazine-2-carboxamide (Example 404, Part D) (0.200 g, 0.777 mmol), 3,3-dimethylbutylamine (0.100 g, 0.777 mmol) and 3 Å molecular sieves in a vial. Add methanol (3.8 mL), cap and stir overnight. Add NaBH4 (in excess over two portions) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 5 g ISCO® pre-load column. Dry the pre-loaded column in a vacuum oven at room temperature. Purify by eluting through a 10 g ISCO® column with (2.0 M NH3 in methanol), ethyl acetate and hexanes. After concentrating, take the product up in CH2Cl2 (25 mL) and wash with 1.0 N NaOH solution (2×10 mL). Dry the organic layer over Na2SO4, filter and concentrate to give the title compound (0.110 g, 41.4%): MS ES+ 343.1 (M+H)+, base peak 242.0 (M-C6H14N)+; HPLC [YMC-Pack Pro 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 19 min], tR=9.7 min, 94.3% purity.

Workup

  1. customDry the pre-loaded column in a vacuum oven at room temperature
  2. customPurify
  3. washby eluting through a 10 g ISCO® column with (2.0 M NH3 in methanol), ethyl acetate and hexanes
  4. concentrationAfter concentrating
  5. washwash with 1.0 N NaOH solution (2×10 mL)
  6. dry with materialDry the organic layer over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate

Sources & evidence

ORD record
ord-db41c4363b46430cb9b949bc51779f72
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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