Imidazole → 5'-O-(tert-butydimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

HRID 500302Notes

Reaction equation

HRID 500302 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]([NH:5][CH2:6][C:7]#[C:8][C:9]1[C:10](=[O:24])[NH:11][C:12](=[O:23])[N:13]([CH:22]=1)[C@@H:14]1[O:21][C@H:18]([CH2:19][OH:20])[C@@H:16]([OH:17])[CH2:15]1)=[O:4].[Si:27](Cl)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].N1C=CN=C1>CN(C=O)C>[Si:27]([O:20][CH2:19][C@H:18]1[O:21][C@@H:14]([N:13]2[CH:22]=[C:9]([C:8]#[C:7][CH2:6][NH:5][C:3](=[O:4])[C:2]([F:25])([F:1])[F:26])[C:10](=[O:24])[NH:11][C:12]2=[O:23])[CH2:15][C@@H:16]1[OH:17])([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 10894132TFA-ap-dU

Product 1

HCID 866642615'-O-(tert-butydimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (1) (656 mg, 1.74 mmol) in dry DMF (15 ml) was added t-butyldimethylsilylchloride (288 mg, 1.91 mmol) in small portions, followed by imidazole (130 mg, 1.91 mmol). The reaction was followed by TLC and was completed after stirring for 8 h at room temperature. The reaction was quenched with sat. aq. NaCl solution. EtOAc (25 ml) was added to the reaction mixture and the aqueous layer was extracted with EtOAc three times. After drying the combined organics (MgSO4), the solvent was removed under vacuum. Purification by chromatography on silica (EtOAc:petroleum ether 8:2) gave (2) as slightly yellow crystals (676 mg, 83%). 1H NMR (d6 DMSO) δ 0.00 (s, 6H, CH3), 0.79 (s, 9H, tBu), 1.93-2.00 (m, 1H, H-2′), 2.06-2.11 (m, 1H, H-2′), 3.63-3.75 (m, 2H, H-5′), 3.79-3.80 (m, 1H, H-4′), 4.12-4.14 (m, 3H, H-3′, CH2N), 5.22 (d, J=4.1 Hz, 1H, OH), 6.03 (t, J=6.9 Hz, 1H, H-1′), 7.86 (s, 1H, H-6), 9.95 (t, J=5.4 Hz, 1H, NH), 11.61 (br s, 1H, NH). Mass (−ve electrospray) calcd for C20H28F3N3O6Si 491.17, found 490.

Workup

  1. customThe reaction was quenched with sat. aq. NaCl solution
  2. additionEtOAc (25 ml) was added to the reaction mixture
  3. extractionthe aqueous layer was extracted with EtOAc three times
  4. dry with materialAfter drying the combined organics (MgSO4)
  5. customthe solvent was removed under vacuum
  6. customPurification by chromatography on silica (EtOAc:petroleum ether 8:2)

Sources & evidence

ORD record
ord-d83707b13b294955a703c93183eb7de0
Source dataset
uspto-grants-2010_08
Patent number
US07771973B2

Reaction notes

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