Triethylamine → HCID 86684722, compound

HRID 339225Notes

Reaction equation

HRID 339225 reaction equation
C(C1C=C(C(C)C)C=C(C(C)C)C=1S(Cl)(=O)=O)(C)C.[Si]([C@@:27]1([OH:68])[C@@H:31]([CH2:32][O:33][Si](C(C)(C)C)(C)C)[O:30][C@@H:29]([N:41]2[CH:48]=[C:47]([CH2:49][O:50][C@H:51]([C:56]3[CH:61]=[C:60]([O:62][CH3:63])[C:59]([I:64])=[CH:58][C:57]=3[N+:65]([O-:67])=[O:66])[C:52]([CH3:55])([CH3:54])[CH3:53])[C:45](=O)[NH:44][C:42]2=[O:43])[CH2:28]1)(C(C)(C)C)(C)C.C([N:71](CC)CC)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[F-]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[I:64][C:59]1[C:60]([O:62][CH3:63])=[CH:61][C:56]([C@@H:51]([O:50][CH2:49][C:47]2[C:45]([NH2:71])=[N:44][C:42](=[O:43])[N:41]([CH:48]=2)[C@@H:29]2[O:30][C@H:31]([CH2:32][OH:33])[C@@H:27]([OH:68])[CH2:28]2)[C:52]([CH3:54])([CH3:55])[CH3:53])=[C:57]([N+:65]([O-:67])=[O:66])[CH:58]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 810422,4,6-Tris(1-methylethyl)benzenesulfonyl chlorideHCID 2724141Tetrabutylammonium FluorideHCID 86684723HCID 86684723, compound

Product 1

HCID 86684722HCID 86684722, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

2,4,6-Triisopropyl benzenesulfonyl chloride (581 mg, 1.92 mmol) was added to a solution of compound 65 (400 mg, 0.48 mmol), DMAP (64 mg, 0.53 mmol), and triethylamine (0.60 mL, 4.32 mmol) in anhydrous CH2Cl2 (15 mL). The mixture was stirred at room temperature overnight under a nitrogen atmosphere, concentrated in vacuo, and the residue was dissolved in a solution of NH3 in 1,4-dioxane (0.5 M, 20 mL). The mixture was transferred into a sealed tube and was heated at 90° C. overnight. The reaction was then cooled to room temperature, concentrated in vacuo, and the residue was dissolved in THF (8.0 mL) followed by addition of n-Bu4NF (333 mg, 1.06 mmol). The mixture was stirred at room temperature for four hours, concentrated in vacuo, and the residue was purified by silica gel column chromatography to yield 5-[(S)-1-(4-iodo-5-methoxy-2-nitrophenyl)-2,2-dimethyl-propyloxy]methyl-2′-deoxycytidine 66 (240 mg, 83% for three steps in total). 1H NMR (400 MHz, MeOD-d4): δ 8.33 (s, 1H, Ph-H), 7.91 (s, 1H, H-6), 7.10 (s, 1H, Ph-H), 6.16 (t, 1H, J=6.4 Hz, H-1′), 5.19 (s, 1H, Ph-CH), 4.41 (d, 1H, J=12.4 Hz, 5-CH2a), 4.33 (m, 1H, H-3′), 4.26 (d, 1H, J=12.4 Hz, 5-CH2b), 3.97 (s, 3H, OCH3), 3.88 (m, 1H, H-4′), 3.70 (m, 2H, H-5′), 2.34 (m, 1H, H-2′a), 2.17 (m, 1H, H-2′b), 0.84 (s, 9H, C(CH3)3).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionthe residue was dissolved in a solution of NH3 in 1,4-dioxane (0.5 M, 20 mL)
  3. customThe mixture was transferred into a sealed tube
  4. temperaturewas heated at 90° C. overnight
  5. temperatureThe reaction was then cooled to room temperature
  6. concentrationconcentrated in vacuo
  7. dissolutionthe residue was dissolved in THF (8.0 mL)
  8. stirringThe mixture was stirred at room temperature for four hours
  9. concentrationconcentrated in vacuo
  10. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-28952ce1b35343bc928d0fe94bbe1044
Source dataset
uspto-grants-2014_11
Patent number
US08889860B2

Reaction notes

Loading…