Acetonitrile → 9-[(2R)2-Deoxy-3,5-di-O-isobutyryl-2-C-ethynyl-2-fluoro-beta-D-erythro-pentofuranosyl]guanine

HRID 2361731

Reaction equation

HRID 2361731 reaction equation
[C:1]([C@@:3]1([F:20])[C@H:7]([OH:8])[CH2:6][O:5][C@H:4]1[N:9]1[CH:17]=[N:16][C:15]2[C:14](=[O:18])[NH:13][C:12]([NH2:19])=[N:11][C:10]1=2)#[CH:2].C(N([CH2:26][CH3:27])CC)C.[C:28]([O:33][C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])(=O)C(C)C.[C:39]([O-:42])(O)=O.[Na+].[C:44](#N)C>CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[C:39]([O:8][C@@H:7]1[C@@H:6]([CH2:28][O:33][C:34](=[O:38])[CH:35]([CH3:36])[CH3:37])[O:5][C@@H:4]([N:9]2[CH:17]=[N:16][C:15]3[C:14](=[O:18])[NH:13][C:12]([NH2:19])=[N:11][C:10]2=3)[C@:3]1([C:1]#[CH:2])[F:20])(=[O:42])[CH:26]([CH3:27])[CH3:44]

Participants

8

Reactant 5

HCID 6342AcetonitrileHCID 7346Isobutyric anhydrideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 1363439289-[(2R)-2-Deoxy-2-C-ethynyl-2-fluoro-beta-D-erythro-furanosyl]-guanine

Product 1

HCID 1361959209-[(2R)2-Deoxy-3,5-di-O-isobutyryl-2-C-ethynyl-2-fluoro-beta-D-erythro-pentofuranosyl]guanine

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 9-[(2R)-2-Deoxy-2-C-ethynyl-2-fluoro-β-D-erythro-furanosyl]guanine (0.16 mmol), 4-dimethylaminopyridine (0.01 mmol), triethylamine (0.48 mmol) and isobutyric anhydride (0.48 mmol), in acetonitrile (1 ml) was stirred at room temperature for 6 hours. The reaction mixture was hydrolysed with a NaHCO3 saturated solution. Ethyl acetate was added. The organic phase was separated, washed with NaCl saturated solution, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by flash column chromatography (DCM/EtOH) to yield the title compound White powder. Molecular Formula C20H24FN5O6 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 1.02-1.22 (m, 12H), 2.53-2.59 (m, 1H), 2.65-2.70 (m, 1H), 4.04 (d, J=4.77 Hz, 1H), 4.35-4.40 (m, 3H), 5.88-5.94 (dd, J=9.39 Hz and J=8.21 Hz, 1H), 6.21-6.25 (d, J=17.28 Hz, 1H), 6.58 (s, 2H), 7.09 (s, 1H), 10.82 (s, 1H). Scan ES+ 450.0 (M+H)+, UV λmax 251 nm

Workup

  1. customThe organic phase was separated
  2. washwashed with NaCl saturated solution
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by flash column chromatography (DCM/EtOH)

Sources & evidence

ORD record
ord-801d79949f21439582fb4f32c3bc1388
Source dataset
uspto-grants-2014_04
Patent number
US08691788B2

Linked notes

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