Bicarbonate Ion → TFA-ap-dC

HRID 500306Notes

Reaction equation

HRID 500306 reaction equation
I[C:2]1[C:3]([NH2:17])=[N:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1.C(N(CC)CC)C.[F:25][C:26]([F:34])([F:33])[C:27]([NH:29][CH2:30][C:31]#[CH:32])=[O:28].N(CO[C@@H]1[C@@H](CO)O[C@@H](N2C=C(C#CCNC(=O)C(F)(F)F)C(=O)NC2=O)C1)=[N+]=[N-].C(=O)(O)[O-]>CN(C=O)C.[Cu]I>[F:25][C:26]([F:34])([F:33])[C:27]([NH:29][CH2:30][C:31]#[C:32][C:2]1[C:3]([NH2:17])=[N:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1)=[O:28]

Participants

8

Reactant 5

HCID 769Bicarbonate IonHCID 8471TriethylamineHCID 65050IbacitabineHCID 110948052,2,2-trifluoro-N-(prop-2-yn-1-yl)acetamideHCID 866136103'-O-Azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

Product 1

HCID 14768553TFA-ap-dC

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-iodo-2′-deoxycytidine (10 g, 28.32 mmol) in DMF (200 ml) in a light protected round bottom flask under Argon atmosphere, was added CuI (1.08 g, 5.67 mmol), triethylamine (7.80 ml, 55.60 mmol), 2,2,2-trifluoro-N-prop-2-ynyl-acetamide (12.8 g, 84.76 mmol) and at last Pd(PPh)3)4 (3.27 g, 2.83 mmol). After 18 hours at room temperature, dowex bicarbonate (20 mg) was added and the mixture was stirred for a further 1 h. Filtration and evaporation of the volatiles under reduced pressure gave a residue that was purified by flash chromatography on silica gel (CH2Cl2, CH2Cl2:EtOAc 1:1, EtOAc:MeOH 9:1). The expected product (7) was obtained as a beige solid in quantitative yield. 1H NMR (D2O) δ 2.24-2.17 (m, 1H, H-2′), 2.41-2.37 (m, 1H, H-2′), 3.68 (dd, J=12.5, 5.0 Hz, 1H, H-5′), 3.77 (dd, J=12.5, 3.2 Hz, 1H, H-5′), 3.99 (m, 1H, H-4′), 4.27 (s, 2H, CH2N), 4.34 (m, 1H, H-3′), 6.11 (t, J=6.3 Hz, 1H, H-1′), 8.1 (br s, 1H, NH); MS (ES): m/z (%) (M−H) 375 (100).

Workup

  1. filtrationFiltration and evaporation of the volatiles under reduced pressure
  2. customgave a residue that
  3. customwas purified by flash chromatography on silica gel (CH2Cl2, CH2Cl2:EtOAc 1:1, EtOAc:MeOH 9:1)

Sources & evidence

ORD record
ord-fa8eae02176b43f4a37a1176455d1e05
Source dataset
uspto-grants-2010_08
Patent number
US07771973B2

Reaction notes

Loading…