Sodium Methoxide → 7-Amino-3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidin-2-one

HRID 1638525Notes

Reaction equation

HRID 1638525 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]([C@@H:8]2[O:30][C@H:29]([CH2:31][O:32]C(=O)C3C=CC=CC=3)[C@@H:19]([O:20]C(=O)C3C=CC=CC=3)[C@H:9]2[O:10]C(=O)C2C=CC=CC=2)[CH:4]2[NH:41][C:42](=[O:44])[S:43][C:3]=12.[NH2:45][C:46]1[C:47]2[S:54][C:53](=[O:55])[N:52]([C@@H:56]3[O:78][C@H:77]([CH2:79][O:80]C(=O)C4C=CC=CC=4)[C@@H:67]([O:68]C(=O)C4C=CC=CC=4)[C@H:57]3[O:58]C(=O)C3C=CC=CC=3)[C:48]=2[N:49]=[CH:50][N:51]=1.C[O-].[Na+]>CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]([C@@H:8]2[O:30][C@H:29]([CH2:31][OH:32])[C@@H:19]([OH:20])[C@H:9]2[OH:10])[CH:4]2[NH:41][C:42](=[O:44])[S:43][C:3]=12.[NH2:45][C:46]1[C:47]2[S:54][C:53](=[O:55])[N:52]([C@@H:56]3[O:78][C@H:77]([CH2:79][OH:80])[C@@H:67]([OH:68])[C@H:57]3[OH:58])[C:48]=2[N:49]=[CH:50][N:51]=1

Participants

6

Reactant 3

HCID 10942334Sodium MethoxideHCID 145057657-Amino-3-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)thiazolo[4,5-d]pyrimidin-2-oneHCID 542120957-amino-4-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2(3H)-one

Product 2

HCID 145057697-Amino-3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidin-2-oneHCID 541349737-amino-4-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidin-2(3H)-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Treatment of 28 with NaSH in DMF at 0° C. yielded the 2-mercapto derivative, 7-aminothiazolo[4,5-d]pyrimidine-2(3H)-thione (29). The conversion of the 2-thioxo function in 29 to a 2-oxo function was accomplished using cold alkaline hydrogen peroxide to yield 7-aminothiazolo[4,5-d]pyrimidin-2(3H)-one (30). Reaction of 30 with the benzoyl-protected sugar, 5, under the same glycosylation conditions (at room temperature) as used to produce the blocked guanosine analog, 6, resulted in the formation of the unexpected blocked 4-ribofuranosyl isomer, 7-amino-4-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2(3H)-one (31), as the only isomer detected and isolated. If, however, the same reaction was carried out at elevated temperature (80° C.), the predominant product obtained was the desired 3-ribofuranosyl isomer, 7-amino-3-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2(3H)-one (32). Both isomers, 31 and 32, were deprotected using sodium methoxide in dry methanol to obtain 7-amino-4-β-D-ribofuranosylthiazolo[4,5-d]pyrimidin-2(3H)-one (33) and 7-amino-3-β-D-ribofuranosylthiazolo[4,5-d]pyrimidin-2(3H)-one (34), respectively.

Workup

  1. customresulted in the formation of the
  2. customisolated
  3. customIf, however, the same reaction
  4. customwas carried out at elevated temperature (80° C.)
  5. customthe predominant product obtained

Sources & evidence

ORD record
ord-e13731bd5d16455791084d002790a184
Source dataset
uspto-grants-1989_11
Patent number
US04880784

Reaction notes

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