Bicarbonate Ion → TFA-ap-dC

HRID 656674Notes

Reaction equation

HRID 656674 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-493407c240024849b2d88dd7cee71800
Source dataset
uspto-grants-2011_12
Patent number
US08071739B2

Reaction notes

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