Sodium hydride → HCID 58071998, compound

HRID 870545Notes

Reaction equation

HRID 870545 reaction equation
[OH:1][CH2:2][C@H:3]1[CH2:7][N:6]([C@@H](C2C=CC=CC=2)C)[C:5](=[O:16])[NH:4]1.[H-].[Na+].Cl[C:20]1[N:29]=[C:28]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[C:32]([O:38][CH3:39])[CH:31]=2)[CH:27]=[C:26]2[C:21]=1[CH:22]=[CH:23][CH:24]=[N:25]2.[CH3:40]C(N(C)C)=O>>[CH3:39][O:38][C:32]1[CH:31]=[C:30]([C:28]2[CH:27]=[C:26]3[C:21]([CH:22]=[CH:23][CH:24]=[N:25]3)=[C:20]([O:1][CH2:2][C@@H:3]3[N:4]([CH3:40])[C:5](=[O:16])[NH:6][CH2:7]3)[N:29]=2)[CH:35]=[CH:34][C:33]=1[O:36][CH3:37]

Participants

5

Reactant 4

HCID 24758Sodium hydride2×HCID 31374Dimethylacetamide2×HCID 58071939HCID 58071939, compoundHCID 58071963HCID 58071963, compound

Product 1

HCID 58071998HCID 58071998, compound

Conditions

Temperature
90 °C

Procedure

174 mg (R)-4-Hydroxymethyl-1-((R)-1-phenyl-ethyl)-imidazolidine-2-one (2.28) was placed in 2 mL dimethylacetamide under nitrogen at ambient temperature before 37.8 mg sodium hydride (60% dispersion in oil) was added. The reaction was stirred for 10 min and then 296 mg 5-chloro-7-(3,4-dimethoxy-phenyl)-[1,6]naphthyridine (6.37) as a solution in 2 mL dimethylacetamide was added. The mixture was heated to 90° C. where it was maintained for 2 h. After this time additional sodium hydride was added and the reaction was stirred at 90° C. for a further 16 h and then at ambient temperature for 3 d. After this time the reaction was heated to 90° C. for 24 h and then it was cooled to ambient temperature. The reaction was quenched by the addition of 5 mL water and extracted with ethyl acetate (×3). The organic fractions were combined, dried over sodium sulfate, filtered and the solvent was removed from the filtrate under reduced pressure. Purification by silica gel chromatography (ethyl acetate/dichloromethane: 5-7% then switching to methanol/ethyl acetate: 10%) provided the title compound.

Workup

  1. additionwas added
  2. temperaturewas maintained for 2 h
  3. stirringthe reaction was stirred at 90° C. for a further 16 h
  4. waitat ambient temperature for 3 d
  5. temperatureAfter this time the reaction was heated to 90° C. for 24 h
  6. temperatureit was cooled to ambient temperature
  7. customThe reaction was quenched by the addition of 5 mL water
  8. extractionextracted with ethyl acetate (×3)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customthe solvent was removed from the filtrate under reduced pressure
  12. customPurification by silica gel chromatography (ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-aa15fdfd2af44fd9a93c36dcba96034c
Source dataset
uspto-grants-2015_03
Patent number
US08969568B2

Reaction notes

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