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

HRID 228329Notes

Reaction equation

HRID 228329 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)=[CH:5][CH:4]=1)=O.[CH3:19][C:20]([CH3:25])([CH3:24])[CH2:21][CH2:22][NH2:23].[BH4-].[Na+]>CO>[CH3:19][C:20]([CH3:25])([CH3:24])[CH2:21][CH2:22][NH:23][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)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 197093,3-DimethylbutylamineHCID 4311764Sodium borohydrideHCID 597301885-(4-Formylphenoxy)pyrazine-2-carboxamide

Product 1

HCID 597301255-{4-[(3,3-Dimethylbutylamino)methyl]phenoxy}pyrazine-2-carboxamideYield 33.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(4-formylphenoxy)pyrazine-2-carboxamide (Example 437, Part B) (0.150 g, 0.617 mmol), 3,3-dimethylbutylamine (0.0624 g, 0.617 mmol) and 3 Å molecular sieves in a vial. Add methanol (3.1 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®0 pre-load column. Dry the 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 dichloromethane (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 (0.0687 g, 33.8%): MS ES+ 329.1 (M+H)+, base peak 228.0 (M-C6H15N)+; 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=9.2 min, 100% purity.

Workup

  1. customDry the 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-412d3f0b0c234691b575515acedfe342
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

Loading…