Dimethylformamide → HCID 58071947, compound

HRID 715722Notes

Reaction equation

HRID 715722 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][CH:17]=[N:18]3)=[C:13]([O:21][CH2:22][C:23]([NH:25][NH2:26])=[O:24])[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].CN(C)[CH:29]=[O:30].C(C1NC=CN=1)(C1NC=CN=1)=O.C(N(CC)CC)C>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][CH:17]=[N:18]3)=[C:13]([O:21][CH2:22][C:23]3[O:24][C:29](=[O:30])[NH:26][N:25]=3)[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471Triethylamine3×HCID 5250894Bis-(1H-imidazol-2-YL)-methanone3×HCID 58071986HCID 58071986, compound

Product 1

HCID 58071947HCID 58071947, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

54 mg [7-(3,4-Dimethoxy-phenyl)-[1,6]-naphthyridine-5-yloxy]-acetic acid hydrazide (I.34) was placed in tetrahydrofuran (10 mL) and N,N-dimethyl formamide (1 mL) at ambient temperature before 37 mg carbonyl diimidazole and 43 μl triethylamine were added. The reaction mixture was heated to 70° C. where it was maintained for 16 h. After this time additional carbonyl diimidazole and triethylamine were added and the reaction was maintained at 70° C. for a further 5 h. After this time additional carbonyl diimidazole and triethylamine were added and the reaction was maintained at 70° C. for a further 19 h. The solvent was then removed under reduced pressure and the crude product that remained was partitioned between dichloromethane and water. The dichloromethane layer was separated and the aqueous phase was extracted with additional dichloromethane (×2). The combined organic fractions were washed with water, saturated sodium chloride solution and then dried over sodium sulfate, filtered and the solvent was removed from the filtrate under reduced pressure. Purification twice by chromatography on silica gel (methanol/ethyl acetate: 0%-5% and then methanol/ethyl acetate: 0%-2%) followed by trituration with dichloromethane provided the title compound.

Workup

  1. temperaturewas maintained for 16 h
  2. temperaturethe reaction was maintained at 70° C. for a further 5 h
  3. temperaturethe reaction was maintained at 70° C. for a further 19 h
  4. customThe solvent was then removed under reduced pressure
  5. customthe crude product that remained was partitioned between dichloromethane and water
  6. customThe dichloromethane layer was separated
  7. extractionthe aqueous phase was extracted with additional dichloromethane (×2)
  8. washThe combined organic fractions were washed with water, saturated sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customthe solvent was removed from the filtrate under reduced pressure
  12. customPurification twice by chromatography on silica gel (methanol/ethyl acetate

Sources & evidence

ORD record
ord-540499e4a82742818089f7725b775a0a
Source dataset
uspto-grants-2015_11
Patent number
US09187478B2

Reaction notes

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