5-(4-[1,3]Dioxolan-2-yl-2-fluorophenoxy)pyrazine-2-carboxamide → 5-(2-Fluoro-4-formylphenoxy)pyrazine-2-carboxamide

HRID 130984Notes

Reaction equation

HRID 130984 reaction equation
[O:1]1CCO[CH:2]1[C:6]1[CH:21]=[CH:20][C:9]([O:10][C:11]2[N:12]=[CH:13][C:14]([C:17]([NH2:19])=[O:18])=[N:15][CH:16]=2)=[C:8]([F:22])[CH:7]=1>C(O)=O>[F:22][C:8]1[CH:7]=[C:6]([CH:2]=[O:1])[CH:21]=[CH:20][C:9]=1[O:10][C:11]1[N:12]=[CH:13][C:14]([C:17]([NH2:19])=[O:18])=[N:15][CH:16]=1

Participants

3

Reactant 1

HCID 597302115-(4-[1,3]Dioxolan-2-yl-2-fluorophenoxy)pyrazine-2-carboxamide

Product 1

HCID 597300135-(2-Fluoro-4-formylphenoxy)pyrazine-2-carboxamideYield 75.7%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

Combine formic acid (90%, 453 mL) and crude 5-(4-[1,3]dioxolan-2-yl-2-fluorophenoxy)pyrazine-2-carboxamide (Example 737, Part D) (32.81 g, approximately 0.09 mole) and stir initially a clear yellow solution, which becomes a thick slurry in an hour at room temperature. Stir overnight at room temperature till the reaction complete by HPLC. Quench the reaction with deionized water (1 L) and extract with dichloromethane (4×4 L). Combine the extracts and mix with aqueous sodium bicarbonate solution. Concentrate on a rotary evaporator to give a slurry of a solid in water (when the separation of layers not possible). Extract the mixture with ethyl acetate (4×1 L) and concentrate the combined extracts to a yellow solid (29.65 g). Form slurries successively four times with boiling methanol (1 L) and filter while hot. Combine the filter cakes and dissolve in enough boiling methanol to give a clear solution. Concentrate the solution to approximately 1 liter and allow to crystallize at 0° C. Filter the resulting slurry at 0° C. and dry the filter cake under vacuum at room temperature to give the title compound (17.79 g, 75.7%). 1H NMR (DMSO-d6) δ 7.70 (t, 1H, ArH), 7.78 (s, 1H, HetH), 7.86-7.93 (m, 2H, ArH), 8.14 (s, 1H, HetH), 8.73 (d, 2H, amide), 10.0 (s, 1H, CHO); 13C NMR (DMSO-d6) δ 116.884, 124.606, 126.980, 133.186, 134.967, 140.765, 144.016, 152.493, 154.974, 159.276, 164.057, 190.777; MS (ES+) m/z 262.3 (M+H).

Workup

  1. customin an hour
  2. customat room temperature
  3. customQuench
  4. customthe reaction with deionized water (1 L)
  5. extractionextract with dichloromethane (4×4 L)
  6. additionCombine the extracts and mix with aqueous sodium bicarbonate solution
  7. concentrationConcentrate on a rotary evaporator
  8. customto give a slurry of a solid in water (when
  9. customthe separation of layers not possible)
  10. extractionExtract the mixture with ethyl acetate (4×1 L)
  11. concentrationconcentrate the combined extracts to a yellow solid (29.65 g)
  12. filtrationForm slurries successively four times with boiling methanol (1 L) and filter while hot
  13. dissolutionCombine the filter cakes and dissolve
  14. customto give a clear solution
  15. concentrationConcentrate the solution to approximately 1 liter
  16. customto crystallize at 0° C
  17. filtrationFilter the resulting slurry at 0° C.
  18. customdry the filter cake under vacuum at room temperature

Sources & evidence

ORD record
ord-65a6d587ec814213987ec6ba0a6f3375
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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