Nitrogen → 3'-O-Azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

HRID 656672Notes

Reaction equation

HRID 656672 reaction equation
[Si]([O:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([C:23]#[C:24][CH2:25][NH:26][C:27](=[O:32])[C:28]([F:31])([F:30])[F:29])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH2:12][C@@H:11]1[O:33][CH2:34]SC)(C(C)(C)C)(C)C.C1CCCCC=1.S(Cl)(Cl)(=O)=O.N#N.[N-:50]=[N+:51]=[N-:52].[Na+]>C(Cl)Cl>[N:50]([CH2:34][O:33][C@@H:11]1[C@@H:10]([CH2:9][OH:8])[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([C:23]#[C:24][CH2:25][NH:26][C:27](=[O:32])[C:28]([F:31])([F:30])[F:29])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH2:12]1)=[N+:51]=[N-:52]

Participants

7

Reactant 5

HCID 947NitrogenHCID 8079CyclohexeneHCID 24648Sulfuryl chlorideHCID 33557Sodium AzideHCID 873394095'-O-(tert-Butydimethylsilyl)-3'-O-methylthiomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

Product 1

HCID 866136103'-O-Azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridineYield 37%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3) (348 mg, 0.63 mmol) and cyclohexene (0.32 ml, 3.2 mmol) in dry CH2Cl2 (5 ml) at 4° C., sulfurylchloride (1M in CH2Cl2, 0.76 ml, 0.76 mmol) was added drop wise under N2. After 10 min TLC indicated the full consumption of the nucleoside (3). The solvent was evaporated and the residue was subjected to high vacuum for 20 min. It was then redissolved in dry DMF (3 ml) and treated with NaN3 (205 mg, 3.15 mmol). The resulting suspension was stirred under room temperature for 2 h. The reaction was quenched with CH2Cl2 and the organic layers were washed with sat aq. NaCl solution. After removing the solvent, the resulting yellow gum was redissolved in THF (2 ml) and treated with TBAF (1 M in THF, 0.5 ml) at room temperature for 30 min. The solvent was removed and the reaction worked up with CH2Cl2 and sat. aq. NaHCO3 solution. The aqueous layer was extracted three times with CH2Cl2. Purification by chromatography on silica (EtOAc:petroleum ether 1:1 to EtOAc) gave (4) (100 mg, 37%) as a pale yellow foam. 1H NMR (d6 DMSO) δ 2.15-2.26 (m, 2H, H-2′), 3.47-3.57 (m, 2H, H-5′), 3.88-3.90 (m, 1H, H-4′), 4.14 (d, J=4.7 Hz, 2H, CH2NH), 4.24-4.27 (m, 1H, H-3′), 4.75 (s, 2H, CH2N3), 5.14 (t, J=5.2 Hz, 1H, OH), 5.96-6.00 (m, 1H, H-1′), 8.10 (s, 1H, H-6), 10.00 (s, 1H, NHCOCF3)), 11.26 (s, 1H, NH).

Workup

  1. customthe full consumption of the nucleoside (3)
  2. customThe solvent was evaporated
  3. waitthe residue was subjected to high vacuum for 20 min
  4. dissolutionIt was then redissolved in dry DMF (3 ml)
  5. customThe reaction was quenched with CH2Cl2
  6. washthe organic layers were washed with sat aq. NaCl solution
  7. customAfter removing the solvent
  8. dissolutionthe resulting yellow gum was redissolved in THF (2 ml)
  9. additiontreated with TBAF (1 M in THF, 0.5 ml) at room temperature for 30 min
  10. customThe solvent was removed
  11. extractionThe aqueous layer was extracted three times with CH2Cl2
  12. customPurification by chromatography on silica (EtOAc:petroleum ether 1:1 to EtOAc)

Sources & evidence

ORD record
ord-0f1319e54d7a42bfb5e9e07eee94954f
Source dataset
uspto-grants-2011_12
Patent number
US08071739B2

Reaction notes

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