Triethylamine → 5-Acetylamino-7-chloro-3-(2,3,5'-tri-O-acetyl-beta-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2-one

HRID 19486Notes

Reaction equation

HRID 19486 reaction equation
P(Cl)(Cl)([Cl:3])=O.[C:6]([NH:9][C:10]1[NH:11][C:12](=O)[C:13]2[S:18][C:17](=[O:19])[N:16]([C@@H:20]3[O:32][C@H:31]([CH2:33][O:34][C:35](=[O:37])[CH3:36])[C@@H:26]([O:27][C:28](=[O:30])[CH3:29])[C@H:21]3[O:22][C:23](=[O:25])[CH3:24])[C:14]=2[N:15]=1)(=[O:8])[CH3:7].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[C:6]([NH:9][C:10]1[N:11]=[C:12]([Cl:3])[C:13]2[S:18][C:17](=[O:19])[N:16]([C@@H:20]3[O:32][C@H:31]([CH2:33][O:34][C:35](=[O:37])[CH3:36])[C@@H:26]([O:27][C:28](=[O:30])[CH3:29])[C@H:21]3[O:22][C:23](=[O:25])[CH3:24])[C:14]=2[N:15]=1)(=[O:8])[CH3:7]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 1355085035-Acetylamino-3-(2,3,5'-tri-O-acetyl-beta-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidine-2,7-dione

Product 1

HCID 865973555-Acetylamino-7-chloro-3-(2,3,5'-tri-O-acetyl-beta-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2-oneYield 90%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
70 °C

Procedure

Phosphorus oxychloride (6.42 mL, 70.2 mmol) was added dropwise to a solution of 16 (3.40 g, 7.02 mmol), triethylamine (1.96 mL, 14.04 mmol), and chloroform (14 mL) over 30 minutes at room temperature under nitrogen. The reaction mixture was then heated to 70° C. for 30 h. The mixture was cooled to ambient temperature, added dropwise over 2 h to a 0° C. solution of saturated aq. NaHCO3 (500 mL), and stirred for an additional 1 h. The layers were separated, aqueous layer back extracted with methylene chloride (2×100 mL), combined organic layers were dried (MgSO4), filtered and concentrated to a yellow solid. Purification was achieved via flash chromatography (SiO2, 5% Acetone-CHCl3) to afford 81 (3.17 g, 90%) as a white solid: 1H NMR (400 MHz, d6-DMSO) δ 11.08 (s, 1H), 6.09 (d, J=4.0 Hz, 1H), 5.99 (dd, J=6.0, 4.0 Hz, 1H), 5.76 (t, J=6.8 Hz, 1H), 4.41 (dd, J=11.2, 3.2 Hz, 1H), 4.32 (td, J=7.2, 3.2 Hz, 1H), 4.24 (dd, J=11.6, 6.8 Hz, 1H), 2.18 (s, 3H), 2.12 (s, 3H), 2.11 (s, 3H), 2.03 (s, 3H); [M+H]+ 503.3.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customThe layers were separated
  3. extractionaqueous layer back extracted with methylene chloride (2×100 mL)
  4. dry with materialwere dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated to a yellow solid
  7. customPurification

Sources & evidence

ORD record
ord-b9faa8e2d0e84f0c944490c4496103db
Source dataset
uspto-grants-2010_06
Patent number
US07745415B2

Reaction notes

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