Diisopropylamine → HCID 58071878, compound

HRID 870543Notes

Reaction equation

HRID 870543 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:16]2[CH:25]=[C:24]3[C:19]([CH:20]=[CH:21][CH:22]=[N:23]3)=[C:18](OS(C(F)(F)F)(=O)=O)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.N[C:35]1[CH:36]=[CH:37][C:38](=[O:41])[NH:39][CH:40]=1.[CH:42]([NH:45]C(C)C)(C)C>CC(N(C)C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:16]2[CH:25]=[C:24]3[C:19]([CH:20]=[CH:21][CH:22]=[N:23]3)=[C:18]([NH:45][CH2:42][C:35]3[CH:36]=[CH:37][C:38](=[O:41])[NH:39][CH:40]=3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]1[CH2:11][CH2:12][O:13][CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 7912Diisopropylamine2×HCID 81825633630-94-32×HCID 58072038HCID 58072038, compound

Product 1

HCID 58071878HCID 58071878, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
70 °C

Procedure

200 mg Trifluoro-methanesulfonic acid 7-[3-methoxy-4-(tetrahydro-pyran-4-yloxy)-phenyl]-[1,6]naphthyridine-5-yl ester (6.6) was placed in 3 mL dimethylacetamide at ambient temperature before 51 mg 5-amino-1H-pyridine-2-one (2.31) and 109 mg N,N-diisopropylamine was added. The reaction was heated to 70° C. overnight in a sealed tube and then cooled to ambient temperature. After this time, additional 5-amino-1H-pyridin-2-one was added and the reaction was heated to 100° C. for 6 h, cooled to ambient temperature overnight. The reaction was then heated again at 100° C. for 24 h and then additional N,N-diisopropylamine was added and heating continued for 24 h. The reaction mixture was then cooled to ambient temperature and partitioned between water and ethyl acetate. The organic phase was separated and the aqueous phase was extracted with additional ethyl acetate (×3) and the combined organic fractions were dried, filtered and the solvent was concentrated from the filtrate under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 95:5) and then by preparative HPLC provided the title compound.

Workup

  1. additionwas added
  2. temperaturecooled to ambient temperature
  3. temperaturethe reaction was heated to 100° C. for 6 h
  4. temperaturecooled to ambient temperature overnight
  5. temperatureThe reaction was then heated again at 100° C. for 24 h
  6. temperatureheating
  7. temperatureThe reaction mixture was then cooled to ambient temperature
  8. custompartitioned between water and ethyl acetate
  9. customThe organic phase was separated
  10. extractionthe aqueous phase was extracted with additional ethyl acetate (×3)
  11. customthe combined organic fractions were dried
  12. filtrationfiltered
  13. concentrationthe solvent was concentrated from the filtrate under reduced pressure
  14. customPurification by silica gel chromatography (ethyl acetate/methanol: 95:5)

Sources & evidence

ORD record
ord-fb41edc8e88d4c98a2cd5a56c418da2d
Source dataset
uspto-grants-2015_03
Patent number
US08969568B2

Reaction notes

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