Nitrous Acid → 7-Amino-2-chlorothiazolo[4,5-d]pyrimidine

HRID 2248926Notes

Reaction equation

HRID 2248926 reaction equation
N[C:2]1[S:3][C:4]2[C:9]([NH2:10])=[N:8][CH:7]=[N:6][C:5]=2[N:11]=1.N(O)=O.[NH2:15][C:16]1[C:17]2[S:24][C:23]([Cl:25])=[N:22][C:18]=2[N:19]=[CH:20][N:21]=1>CN(C=O)C>[NH2:15][C:16]1[C:17]2[S:24][C:23]([Cl:25])=[N:22][C:18]=2[N:19]=[CH:20][N:21]=1.[NH2:10][C:9]1[C:4]2[S:3][C:2](=[S:24])[NH:11][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

6

Reactant 3

HCID 24529Nitrous AcidHCID 10953913Thiazolo[4,5-d]pyrimidine-2,7-diamine2×HCID 145057597-Amino-2-chlorothiazolo[4,5-d]pyrimidine2×

Product 2

HCID 145057597-Amino-2-chlorothiazolo[4,5-d]pyrimidineHCID 145057607-Aminothiazolo[4,5-d]pyrimidine-2(3H)-thione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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.

Sources & evidence

ORD record
ord-2155a563542345e8bfdbff4b79dea029
Source dataset
uspto-grants-1991_08
Patent number
US05041426

Reaction notes

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