Sodium hydride → HCID 53341128, compound

HRID 715706Notes

Reaction equation

HRID 715706 reaction equation
[OH:1][CH2:2][C@H:3]1[CH2:7][NH:6][C:5](=[O:8])[CH2:4]1.[H-].[Na+].Cl[C:12]1[N:21]=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[C:24]([C:35]([F:38])([F:37])[F:36])[CH:23]=2)[CH:19]=[C:18]2[C:13]=1[CH:14]=[CH:15][CH:16]=[N:17]2>CC(N(C)C)=O>[O:32]1[CH2:33][CH2:34][CH:29]([O:28][C:25]2[CH:26]=[CH:27][C:22]([C:20]3[CH:19]=[C:18]4[C:13]([CH:14]=[CH:15][CH:16]=[N:17]4)=[C:12]([O:1][CH2:2][C@H:3]4[CH2:7][NH:6][C:5](=[O:8])[CH2:4]4)[N:21]=3)=[CH:23][C:24]=2[C:35]([F:38])([F:37])[F:36])[CH2:30][CH2:31]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 51669743(4R)-4-(hydroxyMethyl)-2-PyrrolidinoneHCID 58072085HCID 58072085, compound

Product 1

HCID 53341128HCID 53341128, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
70 °C

Procedure

50.7 mg (R)-4-Hydroxymethyl-pyrrolidine-2-one (2.2) was placed in 1.5 mL of dimethylacetamide at ambient temperature under nitrogen before 20.5 mg sodium hydride (60% dispersion in oil) was added. The reaction was stirred for 10 min and then 150 mg 5-chloro-7-[4-(tetrahydro-pyran-4-yloxy)-3-trifluoromethyl-phenyl]-[1,6]naphthyridine (6.23) was introduced and the reaction was heated to 70° C. and stirred overnight. After this time the mixture was cooled to ambient temperature and partitioned between ethyl acetate, water and some saturated sodium chloride solution. The organic layer was separated, dried over sodium sulfate, filtered and the solvent was removed from the filtrate under reduced pressure. Purification by chromatography on silica provided the title compound.

Workup

  1. additionwas added
  2. stirringstirred overnight
  3. temperatureAfter this time the mixture was cooled to ambient temperature
  4. custompartitioned between ethyl acetate, water
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed from the filtrate under reduced pressure
  9. customPurification by chromatography on silica

Sources & evidence

ORD record
ord-dc988ca132544fb59bed25098e72e533
Source dataset
uspto-grants-2015_11
Patent number
US09187478B2

Reaction notes

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