Hydrochloric Acid → HCID 18677530, compound

HRID 1634216Notes

Reaction equation

HRID 1634216 reaction equation
C([NH:4][C:5]1[CH:6]=[C:7]([CH:14]=[C:15]([NH:17]C(=O)C)[N:16]=1)[C:8](N(OC)C)=[O:9])(=O)C.[F:21][C:22]1[CH:27]=[CH:26][C:25]([Mg]Br)=[CH:24][CH:23]=1.Cl>C1COCC1>[NH2:17][C:15]1[CH:14]=[C:7]([C:8]([C:25]2[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=2)=[O:9])[CH:6]=[C:5]([NH2:4])[N:16]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 23552469HCID 23552469, compoundHCID 178418676HCID 178418676, compound

Product 1

HCID 18677530HCID 18677530, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

To a solution of 0.5 g (1.78 mmol) 2,6-bis-acetylamino-N-methoxy-N-methyl-isonicotinamide in 8 ml THF was added at room temperature 7.14 ml (7.14 mmol) of a 1M solution of 4-fluorophenylmagnesium bromide in THF and stirred for 80 min at room temperature and subsequently for 2 h at 40° C. After cooling to room temperature 0.8 ml 37% HCl was added and the mixture was evaporated to dryness. The residue was taken up in ethyl acetate and 2M Na2CO3. The aqueous phase was extracted with ethyl acetate and the combined organic fraction were dried with MgSO4 and evaporated to dryness. The residue was taken up in 3 ml MeOH and 1 ml 37% HCl and heated to reflux for 4 h. After evaporation to dryness the residue was taken up in ethyl acetate and 2M Na2CO3. The aqueous phase was extracted with ethyl acetate and the combined organic fraction were dried with MgSO4 and evaporated to dryness. The title compound was further purified by reversed phase HPLC eluting with an acetonitrile/water gradient and yielded 131 mg (32%) yellow crystals.

Workup

  1. additionwas added
  2. customthe mixture was evaporated to dryness
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. dry with materialthe combined organic fraction were dried with MgSO4
  5. customevaporated to dryness
  6. temperature1 ml 37% HCl and heated
  7. temperatureto reflux for 4 h
  8. customAfter evaporation to dryness the residue
  9. extractionThe aqueous phase was extracted with ethyl acetate
  10. dry with materialthe combined organic fraction were dried with MgSO4
  11. customevaporated to dryness
  12. customThe title compound was further purified by reversed phase HPLC
  13. washeluting with an acetonitrile/water gradient

Sources & evidence

ORD record
ord-49e190a14d7443478c2a790179628898
Source dataset
uspto-grants-2003_01
Patent number
US06506772B1

Reaction notes

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