Ammonia → Adenosine

HRID 1108788Notes

Reaction equation

HRID 1108788 reaction equation
C(O[CH:4]=[N:5][CH:6]1[CH:10]([C:11]#[N:12])[N:9]=[CH:8]P1)C.C([O:21][C@@H:22]1[C@H:26]([O:27]C(=O)C2C=CC=CC=2)[C@@H:25]([CH2:36][O:37]C(=O)C2C=CC=CC=2)[O:24][CH:23]1Br)(=O)C1C=CC=CC=1.[Li].[Li+].CC([N-:52]C(C)C)C.[NH3:56]>>[C@@H:23]1([N:56]2[C:11]3[N:12]=[CH:4][N:5]=[C:6]([NH2:52])[C:10]=3[N:9]=[CH:8]2)[O:24][C@H:25]([CH2:36][OH:37])[C@@H:26]([OH:27])[C@H:22]1[OH:21]

Participants

6

Reactant 5

HCID 222AmmoniaHCID 2724682Lithium diisopropylamideHCID 3028194LithiumHCID 12736014HCID 12736014, compoundHCID 54324847HCID 54324847, compound

Product 1

HCID 60961Adenosine

Procedure

For the synthesis of the target adenosine analog (compound 44), compound 9 serves as a useful starting material. The protection of the amino group is effected by the treatment of compound 9 with diethoxymethylacetate in acetonitrile to give 4-ethoxymethyleneamino-1,3-azaphospholine-5-carbonitrile (compound 41). Coupling of compound 41 with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide (compound 42) (61) provides the corresponding P-nucleoside (compound 43). Compound 43 is also prepared by alkylation of compound 41 with compound 42 in the presence of lithium dusopropylimide (LDA) in a nonpolar solvent at -70° C. This synthetic route is similar to the one used for P-alkylation of 1,3-azaphospholines (62). Compound 43 on reaction with methanolics ammonia (saturated at 0° C.) at room temperature for 24 hours, deprotection of the sugar moiety with concomitant ring cyclization occurs to give the adenosine analog 7-amino-3-(β-D-ribofuranosyl)-1,3-azaphospholo[4,5-d]pyrimidine (compound 44). Compound 44 is also prepared by the direct glycosylation of the sodium salt of compound 14 (generated in situ by the treatment with NaH in CH3CN) with 2,3-O-isopropylidene-5-O-tert-butyldimethylsilyl)-α-D-ribofuranosyl chloride (63) in acetonitrile at room temperature to produce the P-glycosylated product (along with N-glycosylated product), which on separation by flash silica gel column chromatography and deisopropylidenation with aqueous trifluoroacetic acid followed by amination provides compound 44.

Sources & evidence

ORD record
ord-909a70360511477ebd8385f1e7110d6e
Source dataset
uspto-grants-2000_05
Patent number
US06069132

Reaction notes

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