Bromotrimethylsilane → HCID 178420877, compound

HRID 1417168Notes

Reaction equation

P(=O)(O)O.N[C:6]1[N:14]=[C:13]2[C:9]([NH:10][CH:11]=[N:12]2)=[CH:8][N:7]=1.Br[Si](C)(C)C>>[N:7]1[CH:8]=[C:9]2[C:13]([NH:12][CH:11]=[N:10]2)=[N:14][CH:6]=1

Participants

Reactant 2

HCID 76113Bromotrimethylsilane

HCID 178508322HCID 178508322, compound

Product 1

HCID 178420877HCID 178420877, compoundYield 35%

Procedure

Example 1 describes preparation of 2-amino-9-[CR(-)-1-hydroxymethyl-3-diethylphosphono)-1-propyloxymethyl]- 9H-purine 1-5 as shown in Scheme 1. Briefly, the synthesis set forth in Scheme 1 involves, regiospecifically opening 2-(benzyloxymethyl) oxirane 1-1 with lithiated diethyl methylphosphonate in the presence of boron trifluoride etherate to afford 1-2 in 94% yield (Example 1, section (a.)). Compound 1-2 was then transformed to the corresponding chloromethyl ether and condensed with 2-amino-6-chloropurine in the presence of sodium hydride to give the nucleoside phosphonate 1-3 in 53% yield (Example 1, section (b.)). Treatment of 1-3 with 10% palladium/carbon and ammonium formate gave the 2-aminopurine phosphonate 1-4 in 66% yield (Example 1, section (c)). Finally, compound 1-4 was treated with excess bromotrimethylsilane to give the desired nucleoside phosphonate 1-5 in 35% yield (Example 1, section (d.)). Optical purity of compounds was determined by HPLC using a chiral column.

Sources & evidence

ORD record: ord-d42243cc8b9445739d538e0432c6b02d
Source dataset: uspto-grants-1999_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05877166

Reaction notes

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