Methyl iodide → 1,5-anhydro-3-(6-bromo-4-oxo-1,4-dihydrobenzo[h]quinazolin-3(2H)-yl)-2-O-[tert-butyl(dimethyl)silyl]-3,4-dideoxy-L-threo-pentitol

HRID 1183146Notes

Reaction equation

HRID 1183146 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=13)[N:8]=[CH:7][N:6]([C@H:16]1[CH2:21][CH2:20][O:19][CH2:18][C@@H:17]1[O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[C:5]2=[O:30].[H-].[Na+].IC>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=13)[NH:8][CH2:7][N:6]([C@H:16]1[CH2:21][CH2:20][O:19][CH2:18][C@@H:17]1[O:22][Si:23]([C:26]([CH3:28])([CH3:27])[CH3:29])([CH3:24])[CH3:25])[C:5]2=[O:30]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydride2×HCID 86690365HCID 86690365, compound

Product 1

HCID 866903641,5-anhydro-3-(6-bromo-4-oxo-1,4-dihydrobenzo[h]quinazolin-3(2H)-yl)-2-O-[tert-butyl(dimethyl)silyl]-3,4-dideoxy-L-threo-pentitol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of crude 1,5-anhydro-3-(6-bromo-4-oxobenzo[h]quinazolin-3(4H)-yl)-2-O-[tert-butyl(dimethyl)silyl]-3,4-dideoxy-L-threo-pentitol (1.01 g, 2.06 mmol) in DMF (17 mL) was cooled at 0° C. Sodium hydride (95%, 62 mg, 2.58 mmol) was added and the resulting yellow mix was stirred for 5 minutes. Iodomethane (0.27 mL, 4.32 mmol) was added and the reaction was stored in the freezer overnight. LCMS showed the reaction was incomplete. It was put back in an ice bath and additional sodium hydride (50 mg) was added. After 20 minutes, the completed reaction was quenched with ammonium chloride and allowed to warm to room temperature. The reaction was diluted with water and extracted 2× with CH2Cl2. The organics were washed with brine, dried over MgSO4, filtered, concentrated, and dried. The residue was purified via silica gel chromatography, eluting with 10-55% ethyl acetate in hexanes to provide 1,5-anhydro-3-(6-bromo-4-oxo-1,4-dihydrobenzo[h]quinazolin-3(2H)-yl)-2-O-[tert-butyl(dimethyl)silyl]-3,4-dideoxy-L-threo-pentitol that gave a mass ion (ES+) of 506.9 for [M+H]+.

Workup

  1. additionthe resulting yellow mix
  2. customwas stored in the freezer overnight
  3. customIt was put back in an ice bath
  4. waitAfter 20 minutes
  5. customthe completed reaction
  6. customwas quenched with ammonium chloride
  7. additionThe reaction was diluted with water
  8. extractionextracted 2× with CH2Cl2
  9. washThe organics were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customdried
  14. customThe residue was purified via silica gel chromatography
  15. washeluting with 10-55% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-0999c18fdc4743e392b7afd9853dc6e8
Source dataset
uspto-grants-2014_03
Patent number
US08664234B2

Reaction notes

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