Dimethylformamide → HCID 86603473, compound

HRID 2426273Notes

Reaction equation

HRID 2426273 reaction equation
C([O:9][C:10]1[C:15](=[O:16])[N:14]2[CH2:17][CH2:18][CH:19]=[CH:20][C:13]2=[N:12][C:11]=1[C:21]([O:23]C)=O)(=O)C1C=CC=CC=1.CC[N:27]([CH:31](C)C)C(C)C.[F:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39][NH2:40])=[CH:37][CH:36]=1.C(N(CC)CC)C.CN([CH:53]=[O:54])C>>[F:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39][NH:40][C:21]([C:11]2[N:12]=[C:13]3[CH2:20][CH:19]([N:27]([O:54][CH3:53])[CH3:31])[CH2:18][CH2:17][N:14]3[C:15](=[O:16])[C:10]=2[OH:9])=[O:23])=[CH:37][CH:36]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 673264-FluorobenzylamineHCID 81531DiisopropylethylamineHCID 67148094HCID 67148094, compound

Product 1

HCID 86603473HCID 86603473, compound

Conditions

Temperature
65 °C

Procedure

To a solution of methyl 3-(benzoyloxy)-4-oxo-6,7-dihydro-4H-pyrido[1,2-a]pyrimidine-2-carboxylate in anhydrous DMF were added O, N-dimethylhydroxylamine hydrochloride (2.5 eq.) and DIPEA (2.2 eq.). The mixture was stirred and warmed to 65° C. for 6 h. The mixture was cooled to room temperature and the solvent was removed under high vacuum. The residue was dissolved in methanol and p-fluoro-benzylamine (2.2 eq.) and triethylamine (2 eq.) were added. The mixture was stirred at 65° C. for 16 h. After cooling to room temperature the mixture was partitioned between aq. ammonium chloride and dichloromethane. The aq. phase was again extracted with dichloromethane. The combined organic phases were then extracted with 0.1 M NaOH. The aq. phase was then acidified to pH 5 ca. with 1 M aq. HCl and extracted with dichloromethane. The organic phase was dried over sodium sulfate, filtered and concentrated to dryness. The crude product so obtained was used in the subsequent step without further purification.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customthe solvent was removed under high vacuum
  3. dissolutionThe residue was dissolved in methanol
  4. stirringThe mixture was stirred at 65° C. for 16 h
  5. temperatureAfter cooling to room temperature the mixture
  6. customwas partitioned between aq. ammonium chloride and dichloromethane
  7. extractionThe aq. phase was again extracted with dichloromethane
  8. extractionThe combined organic phases were then extracted with 0.1 M NaOH
  9. extractionextracted with dichloromethane
  10. dry with materialThe organic phase was dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-fc9aba8f4c8546c08b9c8637c467b492
Source dataset
uspto-grants-2011_06
Patent number
US07968553B2

Reaction notes

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