Trimethylsilyl iodide → HCID 57947570, compound

HRID 409774Notes

Reaction equation

HRID 409774 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:41])[O:13][CH2:14][C@@H:15]([N:27]([CH3:40])[C:28]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[F:39])=[O:29])[CH2:16][CH2:17][CH2:18][CH2:19][O:20][P:21]([O:25]C)([O:23]C)=[O:22])[N:2]=1.[Si](I)(C)(C)C>C(#N)C>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:41])[O:13][CH2:14][C@@H:15]([N:27]([CH3:40])[C:28]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[F:39])=[O:29])[CH2:16][CH2:17][CH2:18][CH2:19][O:20][P:21]([OH:25])([OH:23])=[O:22])[N:2]=1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 57948010HCID 57948010, compound

Product 1

HCID 57947570HCID 57947570, compoundYield 60.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (S)-2-(3-(2,3-difluorobenzyl)-1-methylureido)-6-(dimethoxyphosphoryloxy)hexyl isoquinolin-3-ylcarbamate (0.28 g, 0.47 mmol, 1.0 equiv.) in acetonitrile (25 mL) was added TMSI (0.28 mL, 1.88 mmol, 4.0 equiv.) at RT After stirred at RT for 15 min, the reaction was quenched with MeOH. The solvent was concentrated. The resulting residue was purified on RP-HPLC using a mixture of acetonitrile and H2O with 0.1% TFA. The fractions containing the product were combined and concentrated. The resulting residue was suspended in EtOAc, 5 drops of HCl (4 M in 1,4-dioxane) were added, and the organic solvent was removed. This procedure was repeated to give (S)-2-(3-(2,3-difluorobenzyl)-1-methylureido)-6-(phosphonooxy)hexyl isoquinolin-3-ylcarbamate (0.16 g, 57%) as a HCl salt. LRMS (M+H+) m/z 567.2.

Workup

  1. customthe reaction was quenched with MeOH
  2. concentrationThe solvent was concentrated
  3. customThe resulting residue was purified on RP-HPLC
  4. additiona mixture of acetonitrile and H2O with 0.1% TFA
  5. additionThe fractions containing the product
  6. concentrationconcentrated
  7. addition5 drops of HCl (4 M in 1,4-dioxane) were added
  8. customthe organic solvent was removed

Sources & evidence

ORD record
ord-3b9cd3e5eb244035bfa589fab494c5fe
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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