Methanethiol → 2'-Deoxy-2'-methylthiouridine

HRID 722760Notes

Reaction equation

HRID 722760 reaction equation
[CH:1]1[C:15](=[O:16])[N:14]=C2[N:3]([C@@H:4]3[O:8][C@H:7]([CH2:9][OH:10])[C@@H:6]([OH:11])[C@@H:5]3O2)[CH:2]=1.[CH3:17][SH:18].[CH3:19]N(C)C(N(C)C)=N>CN(C=O)C>[CH3:19][C@@H:5]1[C@H:6]([OH:11])[C@@H:7]([CH2:9][OH:10])[O:8][C@H:4]1[N:3]1[CH:2]=[CH:1][C:15](=[O:16])[NH:14][C:17]1=[S:18]

Participants

5

Reactant 3

HCID 878MethanethiolHCID 664601,1,3,3-TetramethylguanidineHCID 8061382,2'-Anhydrouridine

Product 1

HCID 1317202082'-Deoxy-2'-methylthiouridineYield 80.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,2′Anhydrouridine (15.5 g, 68.2 mmol) [Rao and Reese, J. Chem. Soc., Chem. Commun., 997], methanethiol (15.7 g, 327 mmol), 1,1,3,3-tetramethylguanidine (39.2 g, 341 mmol) and DMF (150 mL) were heated at 60° C. After 12 hours, the reaction mixture was cooled and concentrated under reduced pressure. The residual oil was purified by flash column chromatography on silica gel (300 g). Concentration of the appropriate fractions, which were eluted with CH2Cl2—MeOH (9:1), and drying the residue under reduced pressure gave 2′-deoxy-2-′-methylthiouridine as a pale yellow solid (14.11 g, 75.4%). Attempts to crystallize the solids from EtOH-hexanes [as reported by Imazawa et al., Chem. Pharm. Bull., 23, 604 (1975)] failed and the material turned into a hygroscopic foam.

Workup

  1. temperaturethe reaction mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. customThe residual oil was purified by flash column chromatography on silica gel (300 g)
  4. washConcentration of the appropriate fractions, which were eluted with CH2Cl2—MeOH (9:1)
  5. customdrying the residue under reduced pressure

Sources & evidence

ORD record
ord-a1f0fef4dd3245379d2e9fd4cbd43cc8
Source dataset
uspto-grants-2006_11
Patent number
US07138517B2

Reaction notes

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