Sodium hydride → HCID 69067543, compound

HRID 1817360Notes

Reaction equation

HRID 1817360 reaction equation
[C:1]([O:5][C:6](=[O:32])[NH:7][C:8]1[N:9]([CH3:31])[C:10](=[O:30])[C:11]([O:28][CH3:29])=[C:12]2[C:17]=1[CH2:16][CH2:15][N:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=1)[C:13]2=[O:27])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:35][S:36](Cl)(=[O:38])=[O:37]>CN(C=O)C>[C:1]([O:5][C:6](=[O:32])[N:7]([C:8]1[N:9]([CH3:31])[C:10](=[O:30])[C:11]([O:28][CH3:29])=[C:12]2[C:17]=1[CH2:16][CH2:15][N:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=1)[C:13]2=[O:27])[S:36]([CH3:35])(=[O:38])=[O:37])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 131727649HCID 131727649, compound

Product 1

HCID 69067543HCID 69067543, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of tert-butyl-[6-(3-chloro-4-fluorobenzyl)-4-methoxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridin-1-yl]carbamate (0.49 g, 1.07 mol) and sodium hydride (54 mg, 1.34 mmol; 60% dispersion in oil) in anhydrous DMF (6 mL) was stirred at 0° C. for 30 minutes. Methanesulfonyl chloride (0.18 g, 1.61 mmol) was added, and the mixture was allowed to warm up slowly to room temperature. The reaction mixture was quenched with aqueous acid and diluted with dichloromethane. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatograph on silica gel eluting with a mixture of 1% methanol in dichloromethane. Collection and concentration of appropriate fractions provided the intermediate tert-butyl-[6-(3-chloro-4-fluorobenzyl)-4-methoxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridin-1-yl](methylsulfonyl)carbamate (ES MS M+1=544). A solution of the above intermediate sulfonylcarbamate (281 mg, 0.52 mmol) and trifluoroacetic acid (5 mL) in anhydrous dichloromethane (5 mL) was stirred at room temperature for 10 minutes. The product mixture was concentrated under vacuum. The residue was partitioned between dichloromethane and aqueous acid. The organic extract was washed dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to provide the title compound. ES MS M+1=444

Workup

  1. temperatureto warm up slowly to room temperature
  2. customThe reaction mixture was quenched with aqueous acid
  3. additiondiluted with dichloromethane
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. additionThe residue was subjected to column chromatograph on silica gel eluting with a mixture of 1% methanol in dichloromethane
  10. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-ec5d8337296441b489b47b5135ef88d4
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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