Sodium borohydride → 5-{4-[(4,4-Dimethylpentylamino)methyl]-2-fluorophenoxy}pyrazine-2-carboxamide

HRID 130995Notes

Reaction equation

HRID 130995 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]([CH3:27])([CH3:26])[CH2:22][CH2:23][CH2:24][NH2:25].[BH4-].[Na+]>CO>[CH3:20][C:21]([CH3:27])([CH3:26])[CH2:22][CH2:23][CH2:24][NH:25][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 4311764Sodium borohydrideHCID 144547574,4-Dimethylpentan-1-amineHCID 597300135-(2-Fluoro-4-formylphenoxy)pyrazine-2-carboxamide

Product 1

HCID 597299545-{4-[(4,4-Dimethylpentylamino)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) (0.400 g, 1.53 mmol), 4,4-dimethylpentylamine (0.194 g, 1.68 mmol) (Example 97, Part B) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (7.7 mL), cap and stir overnight. Add NaBH4 (0.058 g, 1.53 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 0% to 15% (2.0 M NH3 in methanol) in 80% (ethyl acetate in hexanes). Concentrate the fractions containing the product. Take the solid up in dichloromethane (100 mL) and wash with 1.0 N NaOH (2×25 mL) to give the title compound (0.314 g, 57%): TOF MS ES+ 361.2 (M+H)+, HRMS calcd for C19H26N4O2F 361.2040 (M+H)+, found 361.2042, time 0.55 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=12.0 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 0% to 15% (2.0 M NH3 in methanol) in 80% (ethyl acetate in hexanes)
  4. concentrationConcentrate the fractions
  5. additioncontaining the product
  6. washwash with 1.0 N NaOH (2×25 mL)

Sources & evidence

ORD record
ord-1e8558b108f7424381a81d752adbaffc
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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