Adenosine, 5′-(4-methylbenzenesulfonate)

White Crystalline Solid

Dry aziridine (S. Gabriel, Chem. Ber. 1888, 21, 2664-2669; S. Gabriel, R. Stelzner, Chem. Ber. 1895, 28, 2929-2938) (360 l, 7.2 mmol) was added slowly to a suspension of Under a gentle stream of argon, a zirconia-lined jar wassequentially charged with either 5?-chloro-5?-deoxyadenosine (1a, 286 mg, 1.0 mmol)or 5?-O-(p-toluenesulfonyl)adenosine (1b, 421 mg, 1.0 mmol). Subsequently, in quicksuccession, 1, 1, 3, 3-tetramethylguanidine (627 muL, 5.0 mmol, 5 equiv), 4-methoxybenzylthiol (418 muL, 3.0 mmol, 3 equiv) and a 15 mm diameter zirconiaball were added to the jar which was then sealed and vibrated at 30 Hz for either one hour (1a) or 15 minutes (1b) and allowed to cool to ambient temperature. Thecrude reaction mixtures were then extracted from the vessel in MeOH (2 × 25mL) and water (10 mL) and the solution was reduced in vacuo. The residues weretriturated with water (100 mL) under sonication, the suspension was cooled on ice andthe solids were isolated by filtration. The solids were further washed with ice-coldwater (50 mL), dried in vacuo over P2O5 and triturated with 5:1 (v/v) diethyl ether/nhexane (60 mL) under sonication. The suspension was cooled on ice and the solidsisolated following filtration. The solids were washed with ice-cold 5:1 (v/v) diethylether/n-hexane (30 mL) and pure 2a isolated as an amorphous cream/white solidwhich was dried in vacuo.Yield: 310 mg (77percent) ' from 1a; 339 mg (84percent) ' from 1b.Under a gentle stream of argon, two zirconia-lined jars wereeach sequentially charged, in quick succession, with aliquots of5?-O-(p-toluenesulfonyl)adenosine (1b, 126 mg, 0.30 mmol or253 mg, 0.60 mmol), potassium selenocyanate (130 mg, 0.90mmol or 260 mg, 1.8 mmol; 3 equiv), anhydrous DMF (50 muL or 100 muL) and a 15mm diameter zirconia ball. The vessels were vibrated at 30 Hz for eleven hours andallowed to cool to ambient temperature. The reaction mixtures were extracted fromthe vessel in methanol (30 and 50 mL aliquots respectively). Both reaction mixtureswere combined and stirred at room temperature for 30 minutes under argon in thepresence of benzyl bromide (236 muL, 1.98 mmol, 2.2 equiv). The quenched reactionmixture was adsorbed onto silica gel and subject to column chromatography elutingwith 5'15percent (v/v) methanol in DCM. Fractions containing 3a (contaminated with a ptoluene sulphonate salt) were combined and reduced in vacuo. The tosylatecontaminated solids (104 mg) were partitioned between EtOAc (30 mL) and deionisedH2O (15 mL) followed by brine (10 mL). The combined aqueous phases were back-extracted with EtOAc (10 × 10 mL) and the organics combined, dried overNa2SO4 and filtered. The solvent was removed in vacuo to give pure product 3a as awhite amorphous solid.Yield = 65 mg (20percent).

Molecular Weight:421.4
XLogP3:-0.4
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:10
Rotatable Bond Count:5
Exact Mass:421.10560452
Monoisotopic Mass:421.10560452
Topological Polar Surface Area:171
Heavy Atom Count:29
Complexity:670
Defined Atom Stereocenter Count:3
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes