Methanol → 2',3'-Didehydro-3'-deoxy-4'-ethynylthymidine

HRID 215727

Reaction equation

HRID 215727 reaction equation
C([O:4][CH2:5][C@@:6]1([C:25]#[CH:26])[O:10][C@@H:9]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:8][C@H:7]1OS(C)(=O)=O)(=O)C.C1CN2C(=NCCC2)C1.CO>CC#N>[C:25]([C@:6]1([CH2:5][OH:4])[O:10][C@@H:9]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH:8]=[CH:7]1)#[CH:26]

Participants

5

Reactant 3

HCID 887MethanolHCID 763491,5-Diazabicyclo(4.3.0)non-5-eneHCID 865940601-(5-O-Acetyl-2-deoxy-3-O-methanesulfonyl-4-ethynyl-beta-D-threo-pentofuranosyl)thymine

Product 1

HCID 30088972',3'-Didehydro-3'-deoxy-4'-ethynylthymidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 13 (105 mg, 0.272 mmol) and DBN (101 μL, 0.815 mmol) in CH3CN (10 mL) was refluxed for 11 h. After being quenched with AcOH, the reaction mixture was partitioned between CHCl3/saturated aqueous NaHCO3 (60 mL×3/20 mL). The product, obtained after purification by silica gel column chromatography (hexane/EtOAc=1/1) of the organic layer, was dissolved in saturated NH3 in MeOH (30 mL), and kept at room temperature for 12 h. Evaporation of the solvent followed by preparative TLC (hexane/EtOAc=1/1) purification gave TKD-4-114 (49.6 mg, 74%) as a solid: mp 207-209° C.; UV (MeOH) λmax 264 nm (ε10800), λmin 235 nm (ε4800); 1H NMR (CDCl3) δ1.83 (3H, s, Me), 2.63 (1H, s, ethynyl), 3.47 (1H, br, OH), 3.88 (1H, d, Jgem=12.5 Hz, H-5′a), 3.96 (1H, d, Jgem=12.5 Hz, H-5′b), 5.91 (1H, dd, J1′,2′=1.1 Hz and J2′,3′=5.9 Hz, H-2′), 6.30 (1H, dd, J1′,3′=2.0 Hz and J2′,3′=5.9 Hz, H-3′), 7.16-7.17 (1H, m, H-1′), 7.44 (1H, d, J6,Me=1.1 Hz, H-6), 9.06 (1H, br, NH); FAB-MS m/z 249 (M++H). Anal. Calcd for C12H12N2O4.⅙H2O: C, 57.37; H, 4.95; N, 11.15. Found: C, 57.36; H, 4.69; N, 10.98.

Workup

  1. temperaturewas refluxed for 11 h
  2. customAfter being quenched with AcOH
  3. customthe reaction mixture was partitioned between CHCl3/saturated aqueous NaHCO3 (60 mL×3/20 mL)
  4. customThe product, obtained
  5. customafter purification by silica gel column chromatography (hexane/EtOAc=1/1) of the organic layer
  6. dissolutionwas dissolved in saturated NH3 in MeOH (30 mL)
  7. customEvaporation of the solvent
  8. customfollowed by preparative TLC (hexane/EtOAc=1/1) purification
  9. customgave TKD-4-114 (49.6 mg, 74%) as a solid

Sources & evidence

ORD record
ord-63f496c90133404b853a702b17fc867a
Source dataset
uspto-grants-2012_06
Patent number
US08193165B2

Linked notes

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