Trimethylsilyl iodide → HCID 57948021, compound

HRID 416329Notes

Reaction equation

HRID 416329 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([NH:12][C:13](=[O:42])[O:14][CH2:15][C@@H:16]([N:28]([CH3:41])[C:29]([NH:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:34]=1[Cl:40])=[O:30])[CH2:17][CH:18]([OH:27])[CH2:19][O:20][P:21]([O:25]C)([O:23]C)=[O:22])=[CH:5]2.[Si](I)(C)(C)C>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([NH:12][C:13](=[O:42])[O:14][CH2:15][C@@H:16]([N:28]([CH3:41])[C:29]([NH:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:34]=1[Cl:40])=[O:30])[CH2:17][CH:18]([OH:27])[CH2:19][O:20][P:21]([OH:23])([OH:25])=[O:22])=[CH:5]2

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 57947369HCID 57947369, compound

Product 1

HCID 57948021HCID 57948021, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (2S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(dimethoxyphosphoryloxy)-4-hydroxypentyl 6-fluoroisoquinolin-3-ylcarbamate (0.15 g, 0.238 mmol, 1.0 equiv.) in acetonitrile (2 mL) was added TMSI (0.162 mL, 1.19 mmol, 5.0 equiv.) at RT After stirred at RT for 10 min, the reaction was quenched with MeOH. The solvent was removed, and the resulting residue was purified on RP-HPLC using a mixture of acetonitrile and H2O (0.1% TFA buffer) to give the desired product. The product was dissolved in a mixture of methanol and water (2:1), and HCl (4 M in 1,4-dioxane, 2 mL) was added. The solvent was removed. This procedure was repeated to give (2S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-hydroxy-5-(phosphonooxy)pentyl 6-fluoroisoquinolin-3-ylcarbamate (98 mg, 64%) as a HCl salt. LRMS (M+H+) m/z 603.0.

Workup

  1. customthe reaction was quenched with MeOH
  2. customThe solvent was removed
  3. customthe resulting residue was purified on RP-HPLC
  4. additiona mixture of acetonitrile and H2O (0.1% TFA buffer)

Sources & evidence

ORD record
ord-79c4d36cc8f4474581b286d55103cc9d
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

Loading…