Trimethyl Phosphate → 6-Chloropurine riboside-5'-O-monophosphate sodium salt

HRID 928903Notes

Reaction equation

[CH:1]1[N:6]=[C:5]([Cl:7])[C:4]2[N:8]=[CH:9][N:10]([C@@H:11]3[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@H:12]3[OH:19])[C:3]=2[N:2]=1.P(Cl)(Cl)(Cl)=O.[OH-].[NH4+].[P:27](OC)([O:31]C)([O:29]C)=[O:28]>O>[CH:1]1[N:6]=[C:5]([Cl:7])[C:4]2[N:8]=[CH:9][N:10]([C@@H:11]3[O:15][C@H:14]([CH2:16][O:17][P:27]([OH:31])([OH:29])=[O:28])[C@@H:13]([OH:18])[C@H:12]3[OH:19])[C:3]=2[N:2]=1

Participants

Conditions

Temperature: 0 °C

Procedure

6-Chloropurine riboside (100 mg, 0.35 mmol) was dissolved in 1.75 mL of trimethyl phosphate. Phosphoryl chloride (160 mg, 1.05 mmol) was dissolved in a mixture of 0.17 mL of trimethylphosphate and 6.3 μL of water. Both solutions were cooled to 0° C., mixed and stirred on a magnetic stirrer at 0° C. After 6 hours, ice was added to quench the reaction and the pH was adjusted to 7 by addition of ammonium hydroxide solution. The crude product was then concentrated and purified on a C18 reverse phase column using water as the mobile phase. The fractions containing desired product were combined and lyophilized to dryness to afford 6-chloropurine riboside 5′-phosphate (96 mg, 0.26 mmol, 75%) as a white solid. 1H NMR (D2O, 500 MHz) δ (ppm): 4.20 (m, 2H), 4.42 (m, 1H), 4.55 (t, J=4.6 Hz, 1H), 4.84 (m, 1H), 6.28 (d, J=5.1 Hz, 1H), 8.79 (s, 1H), 8.86 (s, 1H).

Workup

additionmixed
additionice was added
customto quench
customthe reaction
concentrationThe crude product was then concentrated
custompurified on a C18 reverse phase column
additionThe fractions containing desired product

Sources & evidence

ORD record: ord-58113b42cf9c4191a6e2da653852ceb4
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290791B2

Reaction notes

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