Sodium hydride → 2-anilino-7-[2-(2-oxo-1-pyrrolidinyl)ethoxy]-1-phenyl-5-(trifluoromethyl)-1,8-naphthyridin-4(1H)-one

HRID 1063549Notes

Reaction equation

HRID 1063549 reaction equation
[H-].[Na+].[OH:3][CH2:4][CH2:5][N:6]1[CH2:10][CH2:9][CH2:8][C:7]1=[O:11].[NH:12]([C:19]1[N:20]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:21]2[C:26]([C:27](=[O:29])[CH:28]=1)=[C:25]([C:30]([F:33])([F:32])[F:31])[CH:24]=[C:23](Cl)[N:22]=2)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CN(C=O)C>[NH:12]([C:19]1[N:20]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:21]2[C:26]([C:27](=[O:29])[CH:28]=1)=[C:25]([C:30]([F:33])([F:32])[F:31])[CH:24]=[C:23]([O:3][CH2:4][CH2:5][N:6]1[CH2:10][CH2:9][CH2:8][C:7]1=[O:11])[N:22]=2)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 769801-(2-Hydroxyethyl)-2-pyrrolidinoneHCID 219481692-anilino-7-chloro-1-phenyl-5-trifluoromethyl-1,8-naphthyridin-4(1H)-one

Product 1

HCID 116204162-anilino-7-[2-(2-oxo-1-pyrrolidinyl)ethoxy]-1-phenyl-5-(trifluoromethyl)-1,8-naphthyridin-4(1H)-oneYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

NaH (60% dispersion, 20.0 mg, 0.514 mmol) was added to a cooled (0° C.) and stirred solution of 1-(2-hydroxyethyl)-2-pyrrolidinone (0.06 mL, 0.514 mmol) in DMF. After 0.5 h, 2-anilino-7-chloro-1-phenyl-5-(trifluoromethyl)-1,8-naphthyridin-4(1H)-one (178 mg, 0.428 mmol) was added as a solid in a single portion and the mixture was heated to 130° C. for 48 h. After cooling to room temperature the mixture was quenched with saturated aqueous NH4Cl and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. Purification by preparative HPLC (10% CH3CN in water with 0.1% TFA to 95% CH3CN in water, 10 mL/min, 10 min) provided 2-anilino-7-[2-(2-oxo-1-pyrrolidinyl)ethoxy]-1-phenyl-5-(trifluoromethyl)-1,8-naphthyridin-4(1H)-one (0.047 g, 64%): LCMS RT: 2.40 min, MH+: 509.2. This transformation can be accomplished by using other aprotic solvents such as DMSO, THF and dioxane with temperatures appropriate for these solvents. Commercially available alkoxides can also be used in the absence of base.

Workup

  1. temperaturethe mixture was heated to 130° C. for 48 h
  2. temperatureAfter cooling to room temperature the mixture
  3. customwas quenched with saturated aqueous NH4Cl
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customPurification by preparative HPLC (10% CH3CN in water with 0.1% TFA to 95% CH3CN in water, 10 mL/min, 10 min)

Sources & evidence

ORD record
ord-8f08a2d2bd47451db862b89a6af49331
Source dataset
uspto-grants-2005_11
Patent number
US06964971B2

Reaction notes

Loading…