2-(Propan-2-yloxy)ethan-1-amine → 5-{4-[(2-Isopropoxyethylamino)methyl]-2-methoxyphenoxy}pyrazine-2-carboxamide

HRID 492621Notes

Reaction equation

HRID 492621 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.[CH:21]([O:24][CH2:25][CH2:26][NH2:27])([CH3:23])[CH3:22].[BH4-].[Na+]>CO>[CH:21]([O:24][CH2:25][CH2:26][NH:27][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]([O:19][CH3:20])[CH:4]=1)([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 5338662-(Propan-2-yloxy)ethan-1-amineHCID 4311764Sodium borohydrideHCID 597299775-(4-Formyl-2-methoxyphenoxy)pyrazine-2-carboxamide

Product 1

HCID 587117625-{4-[(2-Isopropoxyethylamino)methyl]-2-methoxyphenoxy}pyrazine-2-carboxamideYield 55.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(4-formyl-2-methoxyphenoxy)pyrazine-2-carboxamide (Example 719, Part A) (0.700 g, 2.56 mmol), 2-isopropoxyethylamine (0.278 g, 2.69 mmol) and 3 Å molecular sieves in a vial. Add methanol (12.8 mL), cap and stir overnight. Add NaBH4 (0.0969 g, 2.56 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 5% to 20% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes. Concentrate the fraction containing the product, then take it up in EtOAc (100 mL). Wash the organic solution with 1.0 N NaOH (2× 25 mL), dry it over Na2SO4 filter and concentrate to give the title compound (0.512 g, 55.5%): TOF MS ES+ 361.2 (M+H)+, HRMS calcd for C18H25N4O4 361.1876 (M+H)+, found 361.1891, time 0.38 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=9.4 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 5% to 20% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes
  4. concentrationConcentrate the fraction
  5. additioncontaining the product
  6. washWash the organic solution with 1.0 N NaOH (2× 25 mL)
  7. dry with materialdry it over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate

Sources & evidence

ORD record
ord-b149e64481244a2a90ccf89d92ac0220
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

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