134111-32-3 → HCID 10490478, compound

HRID 232532Notes

Reaction equation

HRID 232532 reaction equation
[C@@H:1]1([N:9]2[CH:16]=[CH:15][C:13](=[O:14])[NH:12][C:10]2=[O:11])[S:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1>C(Cl)(Cl)Cl.CO>[C@H:1]1([N:9]2[CH:16]=[CH:15][C:13](=[O:14])[NH:12][C:10]2=[O:11])[S:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1

Participants

3

Reactant 1

HCID 15689273134111-32-3

Product 1

HCID 10490478HCID 10490478, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Procedure

A solution of 1-(2-deoxy-4-thio-3,5-di-O-toluoyl-β-D-ribofuranosyl)uracil (formula 15) (175 mg, 0.36 mmol) in anhydrous MeOH (30 mL) was stirred at room temperature with a freshly prepared solution of sodium methoxide (39 mg, 0.72 mmol) in MeOH (6.5 mL). A TLC aliquot at 2.5 hours showed complete reaction (CHCl3 -MeOH, 95:5). The solution was rendered neutral with Dowex 50W-X8 (H+) ion-exchange resin, the suspension filtered, and the resin was washed with MeOH. The filtrate was combined and evaporated to dryness, and methyl p-toluate was removed at 50° C./0.01 torr. Crystallization of the residue from absolute EtOH gave pure 2'-deoxy-4'-thiouridine (76 mg, 85%); mp 186°-88° C.; TLC 9:1 CHCl3 -MeOH, Rf 0.30; MS z/e 245 (M+1)+, UV λmax pH 1 266 (9.88), pH 7 266 (9.76), pH 13 266 (8.08); 1H NMR (DMSO-d6, 300 MHz) δ2.10-2.22 (m, 2H, H-2'), 3.20-3.34 (m, 1H, H-4'), 3.52-3.62 (m, 2H, H-5'), 4.36 (s, 1H, H-3'), 5.18 (br s, 1H, OH), 5.30 (br s, 1H, OH), 5.68 (d, 1H, H-5, J=8 Hz), 6.26 (t, 1H, H-1', J=7.0 Hz), 8.0 (d, 1H, H-6, J=8 Hz), 11.34 (br s, 1H, H-3). 13C NMR (DMSO-d6, 300 MHz) δ41.246 (C-2'), 58.981 (C-4'), 60.108 (C-1'), 63.465 (C-5'), 73.438 (C-3'), 102.133 (C-5, J=175.92 Hz), 141.354 (C-6, J=180.75 Hz), 150.615 (C-2), 162.743 (C-4). Anal. Calcd. for C9H12N2O4S: C, 44.25; H, 4.95;N, 11.46; S, 13.12. Found: C, 44.20; H, 4.97; N, 11.42; S, 13.03. 1-(2-deoxy-4-thio-3,5-di-O-toluoyl-α-D-ribofuranosyl)uracil was deprotected in a similar manner as described for 2'-deoxy-4'-thiouridine to provide pure 1-(2-deoxy-4-thio-α-D-ribofuranosyl)uracil (75 mg, 85%), mp 190°-192° C.; TLC 9:1 CHCl3 -MeOH, Rf 0.30; MS z/e 245 (M+1)+, UV λmax pH 1 266 (9.24), pH 7 266 (9.52), pH 13 265 (8.72); 1H NMR (Me2SO-d6, 300 MHz) δ2.0-2.28 (m, 1, H-2'), 2.44-2.54 (m, 1H, H-2'), 3.30-3.38 (m, 1H, H-5'), 3.40-3.48 (m, 1H, H-5'), 3.50-3.56 (m, 1H, H-4'), 4.32 (br dd, 1, H-3', J=2 and 8 Hz), 5.64 (d, 1H, H-6, J=8 Hz), 6.14 (dd, 1, H-1', J=3 and 7.5 Hz), 8.26 (d, 1H, H-5, J=8 Hz); 13C NMR (Me2SO-d6, 300 MHz) δ42.16 (C-2), 60.01 (C-4'), 60.95 (C-1'), 63.57 (C-5'), 74.14 (C-3') 101.16 (C-5, JC,H =175.24 Hz), 142.92 (C-6, JC,H =181.88 Hz), 150.69 (C-2), 162.97 (C-4). Anal. Calcd. for C9H12N2O4S: C, 44.25; H, 4.95; N, 11.46; S, 13.12. Found: C, 44.17; H, 4.97; N, 11.39; S, 13.21.

Sources & evidence

ORD record
ord-de0e14711e224c64848a1c409758a111
Source dataset
uspto-grants-1997_01
Patent number
US05591722

Reaction notes

Loading…