Methanethiol → 2'-Deoxy-2'-methylthiouridine

HRID 612839Notes

Reaction equation

HRID 612839 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-ac71f4fd6d2e4e7baac5a2f13f31273c
Source dataset
uspto-grants-1999_12
Patent number
US06005087

Reaction notes

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