2'-Deoxy-2'-fluoro-2'-methyluridine → HCID 45102209, compound
Reaction equation
[F:1][C@:2]1([CH3:18])[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:15]=[CH:14][C:13](=[O:16])[NH:12][C:11]1=[O:17].N1C=NN=N1.C(N([CH:31]([O:39][P:40]([O-])[O-:41])N(C(C)C)C(C)C)C(C)C)(C)C>N1C=CC=CC=1.C(#N)C>[F:1][C@:2]1([CH3:18])[C@@H:6]2[O:7][P@:40]([O:39][CH3:31])(=[O:41])[O:9][CH2:8][C@H:5]2[O:4][C@H:3]1[N:10]1[CH:15]=[CH:14][C:13](=[O:16])[NH:12][C:11]1=[O:17]Participants
Procedure
To a stirred solution of 1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione (730 mg, 2.8 mmol) in dry pyridine (15 mL) was added a 0.45M solution of tetrazole in acetonitrile (15 mL) followed by bis(N,N-diisopropylamino)methylphosphite (0.971 mL, 3.3 mmol) at room temperature. After 2 h, TLC indicated disappearance of the starting material and two non-polar products. The reaction mixture was concentrated under reduced pressure at room temperature and the residue was triturated with EtOAc (30 mL). Tetrazole salts precipitated were filtered off and the filtrate was concentrated under reduced pressure. The residue was chromatographed using 0-40% EtOAc/hexanes gradient to give pure product 2 (92 mg) and mixture of product 1&2 (102 mg). 1H NMR confirmed that the product 2 is a single isomer of the required compound. Stereochemistry is not determined.
Workup
- concentrationThe reaction mixture was concentrated under reduced pressure at room temperature
- customthe residue was triturated with EtOAc (30 mL)
- customTetrazole salts precipitated
- filtrationwere filtered off
- concentrationthe filtrate was concentrated under reduced pressure
- customThe residue was chromatographed
- customto give pure
Sources & evidence
- ORD record
- ord-a11a138ffd5445958ccbda82a7eeb51c
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08173621B2
Reaction notes
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