Methanesulfonyl chloride → HCID 23077506, compound

HRID 1349509Notes

Reaction equation

HRID 1349509 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[CH:9]=[C:10]([CH:39]=[CH:40][C:41]=1[F:42])[CH2:11][NH:12][C:13]([C:15]1[N:16]([CH:31]([CH2:34][O:35][CH2:36][O:37][CH3:38])[CH2:32]O)[CH:17]=[C:18]([Br:30])[C:19](=[O:29])[C:20]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:14].C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O>C(Cl)Cl.C(Cl)(Cl)Cl.C(N(CC)CC)C.CS(C)=O>[CH2:22]([O:21][C:20]1[C:19](=[O:29])[C:18]([Br:30])=[CH:17][N:16]2[C:31]([CH2:34][O:35][CH2:36][O:37][CH3:38])=[CH:32][N:12]([CH2:11][C:10]3[CH:39]=[CH:40][C:41]([F:42])=[C:8]([Cl:7])[CH:9]=3)[C:13](=[O:14])[C:15]=12)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

9

Reactant 4

HCID 31297Methanesulfonyl chloride2×HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 58859191HCID 58859191, compound

Product 1

HCID 23077506HCID 23077506, compoundYield 41.2%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent

Procedure

To a solution of oxalyl chloride (0.245 ml) in methylene chloride (1 ml) was added dropwise a solution of dimethyl sulfoxide (0.269 ml) in methylene chloride (1 ml) under a nitrogen stream at −78° C. and the mixture was stirred for 10 min. A solution of 3-benzyloxy-5-bromo-1-(1-hydroxy-3-methoxymethoxy-2-propyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chloro-4-fluorobenzylamide (410 mg) in methylene chloride (16 ml) was added at the same temperature over 5 min. After stirring for further 10 min after the completion of the dropwise addition, triethylamine (1.37 ml) was added and the mixture was heated to room temperature. The mixture was stirred at room temperature for 1 hr and concentrated. Water was added and the mixture was extracted twice with ethyl acetate. The combined ethyl acetate layer was washed with saturated brine, dried and concentrated. The obtained crude product was dissolved in chloroform (8 ml), and N,N-diisopropylethylamine (0.734 ml) and methanesulfonyl chloride (0.101 ml) were successively added under ice-cooling. After stirring at room temperature for 2 hr, methanesulfonyl chloride (0.05 ml) was added and the mixture was further stirred for 1 hr. The reaction mixture was concentrated, and aqueous sodium hydrogen carbonate solution was added to the residue. The mixture was extracted twice with ethyl acetate. The combined ethyl acetate layer was washed with saturated brine, dried, concentrated and purified by silica gel column chromatography (ethyl acetate:hexane=1:2-ethyl acetate) to give 9-benzyloxy-7-bromo-2-(3-chloro-4-fluorobenzyl)-4-(methoxymethoxy)methyl-2H-pyrido[1,2-a]pyrazine-1,8-dione (163 mg).

Workup

  1. stirringAfter stirring for further 10 min
  2. additionwas added
  3. stirringThe mixture was stirred at room temperature for 1 hr
  4. concentrationconcentrated
  5. additionWater was added
  6. extractionthe mixture was extracted twice with ethyl acetate
  7. washThe combined ethyl acetate layer was washed with saturated brine
  8. customdried
  9. concentrationconcentrated
  10. customThe obtained crude product
  11. temperaturecooling
  12. stirringAfter stirring at room temperature for 2 hr
  13. stirringthe mixture was further stirred for 1 hr
  14. concentrationThe reaction mixture was concentrated
  15. additionaqueous sodium hydrogen carbonate solution was added to the residue
  16. extractionThe mixture was extracted twice with ethyl acetate
  17. washThe combined ethyl acetate layer was washed with saturated brine
  18. customdried
  19. concentrationconcentrated
  20. custompurified by silica gel column chromatography (ethyl acetate:hexane=1:2-ethyl acetate)

Sources & evidence

ORD record
ord-52dd0bef795947dc82c4f05d831cc782
Source dataset
uspto-grants-2007_05
Patent number
US07211572B2

Reaction notes

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