Methanesulfonyl chloride → HCID 23077639, compound

HRID 1349491Notes

Reaction equation

HRID 1349491 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][CH:35]=1)[CH2:5][NH:6][C:7]([C:9]1[N:10]([CH2:30][CH2:31]O)[CH:11]=[C:12]([C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])[C:13](=[O:23])[C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:8].C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.S([O-])(O)(=O)=O.[K+]>O1CCCC1>[CH2:16]([O:15][C:14]1[C:13](=[O:23])[C:12]([C:24](=[O:29])[C:25]([CH3:26])([CH3:28])[CH3:27])=[CH:11][N:10]2[CH2:30][CH2:31][N:6]([CH2:5][C:4]3[CH:33]=[CH:34][CH:35]=[C:2]([Cl:1])[CH:3]=3)[C:7](=[O:8])[C:9]=12)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 516920Potassium bisulfateHCID 58859151HCID 58859151, compound

Product 1

HCID 23077639HCID 23077639, compoundYield 50.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-benzyloxy-5-(2,2-dimethylpropionyl)-1-(2-hydroxyethyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide (91 mg) in tetrahydrofuran (3 ml) was added N,N-diisopropylethylamine (0.187 ml) and the mixture was ice-cooled. Methanesulfonyl chloride (0.07 ml) was added at the same temperature over 30 min with stirring. After confirmation of the completion of the reaction by thin layer chromatography, 5% aqueous potassium hydrogen sulfate solution was added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with brine, aqueous sodium hydrogen carbonate solution and brine, dried and concentrated. The obtained residue was dissolved in dimethylformamide (2 ml) and 60% sodium hydride (50 mg) was added by small portions with stirring at room temperature. After stirring for 30 min, the reaction mixture was ice-cooled and 5% aqueous potassium hydrogen sulfate solution was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried and concentrated. The obtained residue was purified by silica gel thin layer chromatography (ethyl acetate) to give 9-benzyloxy-2-(3-chlorobenzyl)-7-(2,2-dimethylpropionyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,8-dione (44 mg).

Workup

  1. temperaturecooled
  2. additionwas added to the reaction mixture
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed successively with brine, aqueous sodium hydrogen carbonate solution and brine
  5. customdried
  6. concentrationconcentrated
  7. dissolutionThe obtained residue was dissolved in dimethylformamide (2 ml)
  8. addition60% sodium hydride (50 mg) was added by small portions
  9. stirringwith stirring at room temperature
  10. stirringAfter stirring for 30 min
  11. temperaturecooled
  12. addition5% aqueous potassium hydrogen sulfate solution was added
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe ethyl acetate layer was washed with brine
  15. customdried
  16. concentrationconcentrated
  17. customThe obtained residue was purified by silica gel thin layer chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-d6ec5b7547564c8f804cd2ea7d9cfea0
Source dataset
uspto-grants-2007_05
Patent number
US07211572B2

Reaction notes

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