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

HRID 2248927Notes

Reaction equation

HRID 2248927 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

This was circumvented by the synthesis of the adenosine analog from its preformed heterocycle in the same manner as that used to obtain the guanosine analog. The known 2,7-diaminothiazolo[4,5-d]pyrimidine (27) served as the starting material (Scheme V). Treatment of 27 with nitrous acid under conditions similar to those used to prepare 13 provided 7-amino-2-chlorothiazolo[4,5-d]pyrimidine (28). The structure of compound 28 was verified by single-crystal X-ray analysis. 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-414e0105336f4dc08f981306c3400f06
Source dataset
uspto-grants-1991_08
Patent number
US05041426

Reaction notes

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