p-Fluorophenethylamine → HCID 10046273, compound

HRID 228467Notes

Reaction equation

HRID 228467 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.[F:21][C:22]1[CH:30]=[CH:29][C:25]([CH2:26][CH2:27][NH2:28])=[CH:24][CH:23]=1.[BH4-].[Na+]>CO>[F:21][C:22]1[CH:30]=[CH:29][C:25]([CH2:26][CH2:27][NH:28][CH2:1][C:3]2[CH:18]=[CH:17][C:6]([O:7][C:8]3[N:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=3)=[C:5]([O:19][CH3:20])[CH:4]=2)=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 4653p-FluorophenethylamineHCID 4311764Sodium borohydrideHCID 597299775-(4-Formyl-2-methoxyphenoxy)pyrazine-2-carboxamide

Product 1

HCID 10046273HCID 10046273, compoundYield 53.7%

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), 4-fluorophenethylamine (0.374 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 add EtOAc (100 mL). Wash the organic solution with 1.0 N NaOH (2×25 mL), dry it over Na2SO4, filter and concentrate. Dissolve the product in ether:dichloromethane (5:1) (25 mL), add hexanes (20 mL), and then concentrate to about a quarter of the volume. Filter the precipitate to give the title compound (0.545 g, 53.4%): TOF MS ES+ 397.2 (M+H)+, HRMS calcd for C21H22N4O3F 397.1676 (M+H)+, found 397.1689, 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=11.2 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
  10. dissolutionDissolve the product in ether:dichloromethane (5:1) (25 mL)
  11. additionadd hexanes (20 mL)
  12. concentrationconcentrate to about a quarter of the volume
  13. filtrationFilter the precipitate

Sources & evidence

ORD record
ord-6ba4b218d92c4beb8a96735cc9edc205
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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