Diisopropylamine → HCID 53341030, compound

HRID 715707Notes

Reaction equation

HRID 715707 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:22]=[C:21]3[C:16]([CH:17]=[CH:18][CH:19]=[N:20]3)=[C:15](OS(C(F)(F)F)(=O)=O)[N:14]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[NH2:31][CH2:32][C:33]1[O:37][C:36](=[O:38])[NH:35][N:34]=1.C(NC(C)C)(C)C>CC(N(C)C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:22]=[C:21]3[C:16]([CH:17]=[CH:18][CH:19]=[N:20]3)=[C:15]([NH:31][CH2:32][C:33]3[O:37][C:36](=[O:38])[NH:35][N:34]=3)[N:14]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 7912Diisopropylamine2×HCID 24950198HCID 24950198, compoundHCID 58071952HCID 58071952, compound

Product 1

HCID 53341030HCID 53341030, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
70 °C

Procedure

104 mg Trifluoro-methanesulfonic acid 7-(3,4,5-trimethoxy-phenyl)-[1,6]naphthyridine-5-yl ester (6.1), 30 mg (0.261 mmol) of 5-aminomethyl-3H-[1,3,4]oxadiazole-2-one (2.33) and 0.132 mL (0.782 mL) N,N-diisopropylamine were placed in dimethylacetamide at ambient temperature. The reaction was then heated to 70° C. where it was maintained overnight and then cooled to ambient temperature. After this time 0.132 mL (0.782 mL) N,N-diisopropylamine was added and the reaction was heated to 90° C. where it was left for 6 h. The reaction was then cooled to ambient temperature and partitioned between water and ethyl acetate. The organic layer was separated and the aqueous phase was extracted with additional ethyl acetate (×2). The combined organic fractions were dried over sodium sulfate, filtered and the solvent was removed from the filtrate under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 90:10) and then a second purification by silica gel chromatography (dichloromethane/methanol: 100:0 to 95:5) gave the title compound.

Workup

  1. temperaturewas maintained overnight
  2. temperaturecooled to ambient temperature
  3. temperaturethe reaction was heated to 90° C. where it
  4. temperatureThe reaction was then cooled to ambient temperature
  5. custompartitioned between water and ethyl acetate
  6. customThe organic layer was separated
  7. extractionthe aqueous phase was extracted with additional ethyl acetate (×2)
  8. dry with materialThe combined organic fractions were dried over sodium sulfate
  9. filtrationfiltered
  10. customthe solvent was removed from the filtrate under reduced pressure
  11. customPurification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 90:10)
  12. customa second purification by silica gel chromatography (dichloromethane/methanol: 100:0 to 95:5)

Sources & evidence

ORD record
ord-07946498b8b341a3a9a713a665849e92
Source dataset
uspto-grants-2015_11
Patent number
US09187478B2

Reaction notes

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