Methylamine → 5'-Deoxy-5'-N-methylaminoThymidine

HRID 4891Notes

Reaction equation

HRID 4891 reaction equation
C1(C)C=CC(S(O[CH2:11][C@H:12]2[O:16][C@@H:15]([N:17]3[CH:25]=[C:23]([CH3:24])[C:21](=[O:22])[NH:20][C:18]3=[O:19])[CH2:14][C@@H:13]2[OH:26])(=O)=O)=CC=1.[CH3:28][NH2:29].[K+].[Br-]>O>[CH3:28][NH:29][CH2:11][C@H:12]1[O:16][C@@H:15]([N:17]2[CH:25]=[C:23]([CH3:24])[C:21](=[O:22])[NH:20][C:18]2=[O:19])[CH2:14][C@@H:13]1[OH:26]

Participants

5

Reactant 3

HCID 6329Methylamine2×HCID 253877Potassium BromideHCID 7302460((2R,3S,5R)-3-Hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 117771145'-Deoxy-5'-N-methylaminoThymidine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

5'-O-(p-toluenesulfonyl)thymidine (19.8 g, 50 mmol) was placed in a pressure vessel into which monomethylamine (250 g) was condensed. The vessel was sealed and allowed to stand at room temperature for 3 days. The vessel was cooled, opened, and the monomethylamine allowed to evaporate. The remaining contents of the vessel were removed by rinsing with water. The aqueous solution was passed through a column (6.5×20 cm) of AG50Wx8 ion-exchange resin (H+ form). The column was washed with water until the washings were neutral. The product was then eluted with 1N aqueous ammonium hydroxide. The eluent was stripped down and the resulting solid chromatographed on a column (6.5×20 cm) of silica gel with methylene chloride/methanol/concentrated aqueous ammonium hydroxide (85:13:2) as the eluting solvent. The product containing fractions were stripped down, then taken up in water and lyophilized. The product was a pale-yellow, amorphous solid (8.81 g, 69%). A satisfactory combustion analysis could not be obtained for this material.) [α]D25 (c=1.0 in water): +25.9 deg. ir (KBr): cm-1 1693, 1472, 1273, 1076. NMR (DMSO-d6): δ 1.790 (d, 3H), 2.051 (ddd, 13.4, 6.3, 3.5 hz, 1H), 2.142 (dt, 13.4, 6.9 hz, 1H), 2.314 (s, 3H), 2.658 (d, 5.5 hz, 2H), 3.775 (td, 5.3, 3.2 hz, 1H), 4.171 (dt, 6.3, 3.2 hz, 1H), 6.134 (t, 6.9 hz, 1H) and d7.639 (s, 1H).

Workup

  1. customcondensed
  2. customThe vessel was sealed
  3. temperatureThe vessel was cooled
  4. customto evaporate
  5. customThe remaining contents of the vessel were removed
  6. washby rinsing with water
  7. washThe column was washed with water until the washings
  8. washThe product was then eluted with 1N aqueous ammonium hydroxide
  9. customthe resulting solid chromatographed on a column (6.5×20 cm) of silica gel with methylene chloride/methanol/concentrated aqueous ammonium hydroxide (85:13:2) as the eluting solvent
  10. additionThe product containing fractions
  11. customA satisfactory combustion analysis could not be obtained for this material

Sources & evidence

ORD record
ord-4087f7af24ab478188b0f20324748df5
Source dataset
uspto-grants-1993_09
Patent number
US05242796

Reaction notes

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