Trimethylsilyl iodide → HCID 57947564, compound

HRID 416416Notes

Reaction equation

HRID 416416 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:43])[O:14][CH2:15][C@@H:16]([N:29]([CH3:42])[C:30]([NH:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=1[Cl:41])=[O:31])[CH2:17][C:18]([CH3:28])([CH3:27])[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:43])[O:14][CH2:15][C@@H:16]([N:29]([CH3:42])[C:30]([NH:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=1[Cl:41])=[O:31])[CH2:17][C:18]([CH3:27])([CH3:28])[CH2:19][O:20][P:21]([OH:23])([OH:25])=[O:22])=[CH:5]2

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 57947350HCID 57947350, compound

Product 1

HCID 57947564HCID 57947564, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(dimethoxyphosphoryloxy)-4,4-dimethylpentyl 6-fluoroisoquinolin-3-ylcarbamate (0.5 g, 0.79 mmol) in acetonitrile (50 mL) was added TMSI (0.848 mL, 6.23 mmol) at 0° C. After stirred at 0° C. for 30 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 water (0.1% HCOOH buffer) to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4,4-dimethyl-5-(phosphonooxy)pentyl 6-fluoroisoquinolin-3-ylcarbamate (340 mg, 71.1%). LRMS (M+H+) m/z 615.5.

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 water (0.1% HCOOH buffer)

Sources & evidence

ORD record
ord-ddd9ae3807b14fc4998ff2379dee9436
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

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