Bromotrimethylsilane → (4-((6-amino-2-(2-methoxyethoxy)-8-oxo-7H-purin-9(8H)-yl)methyl)benzyl)phosphonic acid

HRID 629933Notes

Reaction equation

[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([O:32]C)[N:6]2[CH2:16][C:17]1[CH:31]=[CH:30][C:20]([CH2:21][P:22](=[O:29])([O:26]CC)[O:23]CC)=[CH:19][CH:18]=1.C[Si](Br)(C)C>C(Cl)Cl>[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[NH:4][C:5](=[O:32])[N:6]2[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:21][P:22](=[O:23])([OH:29])[OH:26])=[CH:30][CH:31]=1

Participants

Conditions

Temperature: 22 °C

Procedure

To a solution of diethyl 4-((6-amino-8-methoxy-2-(2-methoxyethoxy)-9H-purin-9-yl)methyl)benzylphosphonate (1 equiv.) in CH2Cl2 (0.10 M) at 0° C. was slowly added trimethylsilyl bromide (10 equiv.). After 1 h the ice-bath was removed and the reaction mixture was allowed to stir at 22° C. for 2 h. At this point the volatiles were removed in vacuo and the resulting residue was purified by Reverse Phase-HPLC using a 20-90% 0.5 mM NH4OAc (in MeCN) to 10 mM NH4OAc (in water) gradient to deliver the title compound (29%) as a solid.

Workup

customat 0° C.
customAfter 1 h the ice-bath was removed
customAt this point the volatiles were removed in vacuo
customthe resulting residue was purified by Reverse Phase-HPLC

Sources & evidence

ORD record: ord-fc4d80e084ea414283b47a993ef21f32
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315530B2

Reaction notes

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