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

HRID 228439Notes

Reaction equation

HRID 228439 reaction equation
[F:1][C:2]1[CH:17]=[C:16]([CH:18]=O)[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[N:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=1.[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][CH2:18][C:16]1[CH:15]=[CH:14][C:3]([O:4][C:5]2[N:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=2)=[C:2]([F:1])[CH:17]=1

Participants

5

Reactant 3

HCID 197093,3-DimethylbutylamineHCID 4311764Sodium borohydrideHCID 597300135-(2-Fluoro-4-formylphenoxy)pyrazine-2-carboxamide

Product 1

HCID 103376835-{4-[(3,3-Dimethylbutylamino)methyl]-2-fluorophenoxy}pyrazine-2-carboxamideYield 57%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(2-fluoro-4-formylphenoxy)pyrazine-2-carboxamide (Example 737, Part E) (0.350 g, 1.14 mmol), 3,3-dimethylbutylamine (0.19 g, 1.41 mmol) and 3 Å molecular sieves in a vial. Add methanol (9.7 mL), cap and stir overnight. Add NaBH4 (0.053 g, 1.41 mmol) and stir until the gasses stop evolving. Filter the reaction mixture, then concentrate. Purify by eluting through a 40 g ISCO® column with 6% to 30% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.225 g, 49%): TOF MS ES+ 347.2 (M+H)+, HRMS calcd for C18H24N4O2F 347.1883 (M+H)+, found 347.1883, time 0.53 min; HPLC [YMC-Pro pack C-18 (150×4.6 min, 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=10.9 min, 100% purity.

Workup

  1. filtrationFilter the reaction mixture
  2. concentrationconcentrate
  3. customPurify
  4. washby eluting through a 40 g ISCO® column with 6% to 30% (2.0 M NH3 in methanol) in ethyl acetate

Sources & evidence

ORD record
ord-fbdf19c4bcb7413789928ce6d9bdb5a0
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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