N-Methylcarbazole → HCID 14697458, compound

HRID 1649881Notes

Reaction equation

HRID 1649881 reaction equation
CN1C2C=CC=CC=2C2C1=CC=CC=2.[S:15]([O:19][C@H:20]1[C@@H:24]([CH2:25][O:26][C:27]([O:29][CH3:30])=[O:28])[O:23][C@@H:22]([N:31]2[CH:39]=[C:37]([CH3:38])[C:35](=[O:36])[NH:34][C:32]2=[O:33])[C@@H:21]1OC(=O)C1C=CC=C(C(F)(F)F)C=1)([CH3:18])(=[O:17])=[O:16]>C(O)(C)C>[S:15]([O:19][C@H:20]1[C@@H:24]([CH2:25][O:26][C:27]([O:29][CH3:30])=[O:28])[O:23][C@@H:22]([N:31]2[CH:39]=[C:37]([CH3:38])[C:35](=[O:36])[NH:34][C:32]2=[O:33])[CH2:21]1)([CH3:18])(=[O:16])=[O:17]

Participants

4

Reactant 2

HCID 15142N-MethylcarbazoleHCID 14697456HCID 14697456, compound

Product 1

HCID 14697458HCID 14697458, compoundYield 68.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A 500 mL pyrex photochemical reaction vessel equipped with a nitrogen inlet, magnetic stirrer, reflux condenser, quartz immersion well and a 450 watt medium pressure mercury-vapor immersion lamp surrounded by a uranium absorption sleeve was charged with 90% aqueous isopropyl alcohol (500 mL), N-methyl carbazole (1.46 g, 8.05 mmoles) and 1-(3-O-mesyl-5-O-(methoxycarbonyl)-2-O-(m-trifluoromethyl-benzoyl)-β-D-xylofuranosyl)thymine (3.80 g, 6.71 mmoles) from Example A3. After bubbling nitrogen through the solution for 45 minutes the solution was photolyzed for 20 hours. The solvent was concentrated to a 50 mL volume by rotary evaporation and the remaining liquid was diluted with chloroform (300 mL). The organic solution was washed with 10% aqueous NaHCO3 (2×200 ml) and the solvent was removed by rotary evaporation. The residual oil was purified by flash chromatography (3-inch diameter column containing 15 inches of flash silica gel). The column was eluted with 95:5/CHCl3 :CH3OH while collecting 125 mL fractions. Fractions 15-19 contained pure product and these fractions were concentrated in vacuo affording 1.75 g (68.9%) of 1-[2-deoxy-3-O-mesyl-5-O-methoxycarbonyl-β-D-threo-pentofuranosyl]thymine as a white crystalline solid. mp: 70°-72° C.; TLC Rf =0.51. Silica gel, CHCl3 : CH3OH/90/10

Workup

  1. customA 500 mL pyrex photochemical reaction vessel equipped with a nitrogen inlet, magnetic stirrer
  2. temperaturereflux condenser
  3. customquartz immersion well and a 450 watt medium pressure mercury-vapor immersion lamp surrounded by a uranium absorption sleeve
  4. customAfter bubbling nitrogen through the solution for 45 minutes the solution
  5. concentrationThe solvent was concentrated to a 50 mL volume by rotary evaporation
  6. additionthe remaining liquid was diluted with chloroform (300 mL)
  7. washThe organic solution was washed with 10% aqueous NaHCO3 (2×200 ml)
  8. customthe solvent was removed by rotary evaporation
  9. customThe residual oil was purified by flash chromatography (3-inch diameter column containing 15 inches of flash silica gel)
  10. washThe column was eluted with 95:5/CHCl3
  11. customCH3OH while collecting 125 mL fractions
  12. concentrationFractions 15-19 contained pure product and these fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-1cb000ee50924fc0bb4f1ddc11d4784e
Source dataset
uspto-grants-1990_05
Patent number
US04921950

Reaction notes

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