Phenyl thioxochloroformate → 9-(3,5-Di-O-benzoyl-2-deoxy-beta-L-threo-pentofuranosyl)adenine

HRID 1937368Notes

Reaction equation

HRID 1937368 reaction equation
[C:1]([O:9][C@@H:10]1[C@H:14]([CH2:15][O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:13][C@H:12]([N:25]2[CH:33]=[N:32][C:31]3[C:26]2=[N:27][CH:28]=[N:29][C:30]=3[NH2:34])[C@H:11]1O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O(C(Cl)=S)C1C=CC=CC=1.[H-].C[Si]([SiH]([Si](C)(C)C)[Si](C)(C)C)(C)C>C(#N)C.CN(C)C1C=CN=CC=1.O1CCOCC1>[C:1]([O:9][C@@H:10]1[C@H:14]([CH2:15][O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:13][C@H:12]([N:25]2[CH:33]=[N:32][C:31]3[C:26]2=[N:27][CH:28]=[N:29][C:30]=3[NH2:34])[CH2:11]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 70498Phenyl thioxochloroformateHCID 667172129-(3,5-Di-O-benzoyl-beta-L-xylofuranosyl)adenineHCID 131723225Tris-(trimethylsilyl)silane hydride

Product 1

HCID 120709949-(3,5-Di-O-benzoyl-2-deoxy-beta-L-threo-pentofuranosyl)adenineYield 96%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of compound 3 (1.00 g, 2.11 mmol) in dry acetonitrile (65 mL) were added 4-(dimethylamino)pyridine (0.77 g, 6.32 mmol) and phenoxythiocarbonyl chloride (0.44 mL, 3.16 mmol). The mixture was stirred at room temperature for 2 h. After concentration, the residue was dissolved in dichloromethane (50 mL) and washed successively with water (2×30 mL), aqueous solution of hydrochloric acid 0.5 N (30 mL) and water (3×30 mL). The organic layer was dried, filtered and concentrated to dryness. The crude thiocarbonylated intermediate was directly treated with tris-(trimethylsilyl)silane hydride (0.78 mL, 5.23 mmol) and α,α′-azoisobutyronitrile (AIBN, 0.112 g, 0.69 mmol) in dry dioxane (17 mL) at reflux for 2 h. The solvent was removed under vacuum and the residue was purified by silica gel column chromatography (0-5% MeOH in dichloromethane) to give pure 4 (0.93 g, 96%) as a foam: 1H NMR (DMSO-d6): δ2.9-3.1 (m, 2H, H-2′ and H-2″), 4.6-4.7 (m, 3H, H-4′, H-5′ and H-5″), 5.8 (br s, 1H, H-3′), 6.43 (dd, 1H, H-1′, J1′,2′=3.1 Hz, J1′,2″=7.6 Hz), 7.3 (br s, 2H, NH2-6), 7.4-7.9 (m, 10H, 2 benzoyls), 8.05 and 8.33 (2s, 2H, H-2 and H-8); ms : matrix G/T, (FAB+) m/z 460 [M+H]+, 325 [S]+, 136 [BH2]+, (FAB−) m/z 458 [M−H]−, 134 [B]−; UV (95% ethanol): λmax 261 nm (ε 14400), 231 nm (ε 26300), λmin 249 nm (ε 12000); [α]D20=−38 (c 1.04, DMSO).

Workup

  1. concentrationAfter concentration
  2. dissolutionthe residue was dissolved in dichloromethane (50 mL)
  3. washwashed successively with water (2×30 mL), aqueous solution of hydrochloric acid 0.5 N (30 mL) and water (3×30 mL)
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. temperatureat reflux for 2 h
  8. customThe solvent was removed under vacuum
  9. customthe residue was purified by silica gel column chromatography (0-5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-00cbfe8c69f64ba18d1bdd9a4e7dd6f9
Source dataset
uspto-grants-2002_05
Patent number
US06395716B1

Reaction notes

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