Methanethiol → 2'-Deoxy-2'-methylthiouridine

HRID 381690Notes

Reaction equation

HRID 381690 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)C=O>[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, T. S. and Reese, C. B. (1989) J. Chem. Soc., Chem. Commun., 997], methanethiol (15.7 g, 327 mmol), 1,1,3,3-tetramethylguanidine (39.2 g, 341 mmol) and dimethylforamide (150 ml) were heated together at 60° C. After 12 hr, 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, v/v), and drying of the residue under high vacuum gave 2′-deoxy-2′-methylthiouridine as a pale yellow solid (14.11 g, 75.4%). Attempts to crystallize the solids from ethanol-hexanes (as reported by Imazawa, M., Ueda, T., and Ukita, T. (1975) Chem. Pharm. Bull., 23:604) 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, v/v)
  5. customdrying of the residue under high vacuum

Sources & evidence

ORD record
ord-c0b07e3e95dd4b58908b357ebee70b75
Source dataset
uspto-grants-2001_10
Patent number
US06307040B1

Reaction notes

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