Ethyl Thioglycolate → Ethyl {[7-anilino-5-oxo-8-phenyl-4-(trifluoromethyl)-5,8-dihydro-1,8-naphthyridin-2-yl]sulfanyl}acetate

HRID 2215010Notes

Reaction equation

HRID 2215010 reaction equation
[H-].[Na+].[SH:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[NH:10]([C:17]1[N:18]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:19]2[C:24]([C:25](=[O:27])[CH:26]=1)=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:22]=[C:21](Cl)[N:20]=2)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>CN(C=O)C>[NH:10]([C:17]1[N:18]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:19]2[N:20]=[C:21]([S:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH:22]=[C:23]([C:28]([F:31])([F:30])[F:29])[C:24]=2[C:25](=[O:27])[CH:26]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 12185Ethyl ThioglycolateHCID 24758Sodium hydrideHCID 219481692-anilino-7-chloro-1-phenyl-5-trifluoromethyl-1,8-naphthyridin-4(1H)-one

Product 1

HCID 11684737Ethyl {[7-anilino-5-oxo-8-phenyl-4-(trifluoromethyl)-5,8-dihydro-1,8-naphthyridin-2-yl]sulfanyl}acetateYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

NaH (60% dispersion in oil, 18.0 mg, 0.434 mmol) was added to a cooled (0° C.) and stirred solution of ethyl mercaptoacetate (0.05 mL, 0.434 mmol) in DMF. After 0.5 h, 2-anilino-7-chloro-1-phenyl-5-(trifluoromethyl)-1,8-naphthyridin-4(1H)-one (150.0 mg, 0.361 mmol) was added as a solid in a single portion. The mixture was allowed to warm to room temperature and was stirred for 24 h. The reaction was quenched with water 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 ethyl {[7-anilino-5-oxo-8-phenyl-4-(trifluoromethyl)-5 ,8-dihydro-1,8-naphthyridin-2-yl]sulfanyl}acetate (50 mg, 53%): LCMS RT: 3.91 min, MH+: 500.2, R=0.24 (1:1 EtOAc:Hex).

Workup

  1. temperatureto warm to room temperature
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. 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-6441d7dcd28845fbbfc0eb9a2564b43a
Source dataset
uspto-grants-2006_09
Patent number
US07109196B2

Reaction notes

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