Dimethyl Sulfoxide → N6-benzoyl-3'-O-(methylthiomethyl)-5'-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine

HRID 58508Notes

Reaction equation

HRID 58508 reaction equation
[C:1]([NH:9][C:10]1[C:11]2[N:12]=[CH:13][N:14]([C:30]=2[N:31]=[CH:32][N:33]=1)[C@@H:15]1[O:29][C@H:19]([CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[C@@H:17]([OH:18])[CH2:16]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:34][S:35]([CH3:37])=O.C(OC(=O)C)(=O)C.C([O-])(O)=O.[Na+]>C(O)(=O)C>[C:1]([NH:9][C:10]1[C:11]2[N:12]=[CH:13][N:14]([C:30]=2[N:31]=[CH:32][N:33]=1)[C@@H:15]1[O:29][C@H:19]([CH2:20][O:21][Si:22]([C:25]([CH3:26])([CH3:27])[CH3:28])([CH3:24])[CH3:23])[C@@H:17]([O:18][CH2:34][S:35][CH3:37])[CH2:16]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 13833804N-(9-((2R,4S,5R)-5-((Tert-butyldimethylsilyloxy)methyl)-4-hydroxytetrahydrofuran-2-YL)-9H-purin-6-YL)benzamide

Product 1

HCID 11813430N6-benzoyl-3'-O-(methylthiomethyl)-5'-O-(tert-butyldimethylsilyl)-2'-deoxyadenosineYield 71%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

3.0 g N6-Benzoyl-5′-O-tert-butyldimethylsilyl-2′-deoxyadenosine (5a) (6.38 mmol) was dissolved in a mixture consisting of 11.96 mL DMSO, 5.46 mL acetic acid, and 17.55 mL acetic anhydride and stirred at room temperature for 48 h. The reaction mixture was then neutralized treating with a sufficient amount of saturated NaHCO3 solution and extracted with CH2Cl2 (3×100 mL). The combined organic extract was then washed with a saturated NaHCO3 solution (100 mL), dried over Na2SO4, and concentrated under vacuum. The resultant yellowish oil was then purified on silica gel column (Hex: EtOAc/1:1 to 1:4) to obtain the product N6-benzoyl-3′-O-(methylthiomethyl)-5′-O-(tert-butyldimethylsilyl)-2′-deoxyadenosine (6a) as white powder in 71% yield (2.4 g, Rf 0.6, EtOAc: hex/7:3). HR-MS: obs. m/z 530.2273, calcd. for C25H36O4N5SiS 530.2257 [M+H]+. 1H-NMR (CDCl3): δH 9.00 (s, 1H), 8.83 (s, 1H), 8.35 (s, 1H), 8.05 (d, J=7.6 Hz, 2H), 7.62 (m, 1H), 7.55 (m, 2H), 6.55 (t, J=7.19 Hz, 1H), 4.73 (m, 2H), 4.68 (m, 1H), 4.24 (m, 1H), 3.88 (dd, J=11.19, 3.19 Hz, 1H), 2.74-2.66 (m, 2H), 2.35 (s, 3H), 0.94 (s, 9H) and 0.13 (s, 6H) ppm.

Workup

  1. extractionextracted with CH2Cl2 (3×100 mL)
  2. extractionThe combined organic extract
  3. washwas then washed with a saturated NaHCO3 solution (100 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe resultant yellowish oil was then purified on silica gel column (Hex: EtOAc/1:1 to 1:4)

Sources & evidence

ORD record
ord-e09ec41a72e4436f8eb4ce6bc57d9702
Source dataset
uspto-grants-2016_09
Patent number
US09434989B2

Reaction notes

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