Dimethylformamide → 2',5'-Dideoxyadenosine

HRID 1824660Notes

Reaction equation

HRID 1824660 reaction equation
[P].C[O:3][C:4]1[CH:5]=CC(C=O)=[CH:8][CH:9]=1.[NH:12]1[CH:16]=NN=N1.C1(C)C=C(C)C=C(C)C=1S([N:28]1[CH:32]=[N:31][C:30]([N+:33]([O-])=O)=N1)(=O)=O.[CH3:37][N:38]([CH3:41])[CH:39]=[O:40]>O.[O-][Mo]([O-])(=O)=O.O1CCCC1.N1C=CC=CC=1.C(#N)C>[C@@H:39]1([N:38]2[C:41]3[N:28]=[CH:32][N:31]=[C:30]([NH2:33])[C:16]=3[N:12]=[CH:37]2)[O:40][C@H:9]([CH3:8])[C@@H:4]([OH:3])[CH2:5]1

Participants

11

Reactant 5

HCID 6228DimethylformamideHCID 312444-MethoxybenzaldehydeHCID 7169013-Nitro-1-(2,4,6-trimethylbenzene-1-sulfonyl)-1H-1,2,4-triazoleHCID 5462309PhosphorusHCID 178418441HCID 178418441, compound

Product 1

HCID 651662',5'-Dideoxyadenosine

Reagents, catalysts & solvents 5

HCID 24621Molybdate ionCatalystHCID 962WaterSolventHCID 1049PyridineSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

General methods for synthesis of compounds 1-3 and 7-17. 31P (101 MHz) and 1H NMR (250 MHz): Bruker AC250; the residual solvent peaks were used as internal standard for the 1H NMR spectra, phosphoric acid was used as external standard for the 31P NMR spectra. All 31P NMR spectra were recorded in the proton-decoupled mode. Chemical shifts are given in δ (ppm) and coupling constants, J, are in Hz. Column chromatography was carried out on silica gel 60 (particle size 0.040-0.063 mm; EM Science, Merck, Darmstadt). Analytical thin-layer chromatography, used to monitor all reactions, was performed on silica get 60 PF254, with fluorescence indicator (0.2 mm; Merck, Darmstadt) on aluminum plates, and visualization was accomplished by UV absorbance. Phosphorus containing compounds were detected by spraying with Hanes molybdate reagent. Sugar containing compounds were detected by spraying with anisaldehyde reagent each time followed by heating. High-performance liquid chromatography (HPLC) studies were carried out on a Waters system equipped with a model 600 controller, a model 717plus autosampler, a model 996 photodiode array detector and a Millenium data workstation. Separations were by reverse-phase chromatography (Ultrasphere, C18, 250×4.6 mm, 5 μm) with linear gradients of 0 to 100% acetonitrile in water over a 40 min period at a flow rate of 1 ml/min. S-acyl-2-thioethanols and bis(S-2-hydroxyethylthioacyl) N,N-diisopropylphosphoramidites were synthesized according to Lefebvre et al.[50]. The cyclic chlorophosphanes were synthesized according to Meier [51]. 2′,5′-dideoxyadenosine was synthesized according to Désaubry et al. [52]. Monotriethylammonium N6-(4-monomethoxytrityl)-9-(2-phosphonylmethoxypropyl)-adenine was synthesized according to Holy et al. [53,54]. Solvents: pyridine, tetrahydrofuran and dimethylformamide were analytical quality, absolute from Fluke. 1H-tetrazole and 1-(mesitylenesulfonyl)-3-nitro-1H-1,2,4-triazole were from Aldrich.

Workup

  1. temperatureby heating
  2. customequipped with a model 600 controller
  3. customover a 40 min
  4. customS-acyl-2-thioethanols and bis(S-2-hydroxyethylthioacyl) N,N-diisopropylphosphoramidites were synthesized
  5. customThe cyclic chlorophosphanes were synthesized

Sources & evidence

ORD record
ord-dcda71651b5b4e00abc9a8f08d940404
Source dataset
uspto-grants-2006_05
Patent number
US07045309B2

Reaction notes

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