Trimethylsilyl iodide → (S)-3-amino-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl isoquinolin-3-ylcarbamate

HRID 340996Notes

Reaction equation

HRID 340996 reaction equation
C(OC([NH:11][CH2:12][C@H:13]([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])[CH2:14][O:15][C:16](=[O:28])[NH:17][C:18]1[N:19]=[CH:20][C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[CH:23][CH:22]=2)=O)C1C=CC=CC=1.[Si](I)(C)(C)C>CC#N>[CH:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:27]=[C:18]([NH:17][C:16](=[O:28])[O:15][CH2:14][C@@H:13]([N:29]([CH3:42])[C:30]([NH:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=2[Cl:41])=[O:31])[CH2:12][NH2:11])[N:19]=1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 57947695Isoquinolin-3-yl-carbamic acid (S)-3-benzyloxycarbonylamino-2-[3-(2-chloro-3-fluoro-benzyl)-1-methyl-ureido]-propyl ester

Product 1

HCID 57947642(S)-3-amino-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl isoquinolin-3-ylcarbamateYield 275.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of isoquinolin-3-yl-carbamic acid (S)-3-benzyloxycarbonylamino-2-[3-(2-chloro-3-fluoro-benzyl)-1-methyl-ureido]-propyl ester (1.3 g, 2.13 mmol) in CH3CN (20.0 mL) was added TMSI (0.35 mL, 2.56 mmol). The mixture was stirred at RT for 15 min and quenched with MeOH (20.0 mL). The resulting mixture was stirred for another 15 min, concentrated to dryness, and partitioned in between ether (30 mL) and HCl (2 N, 20 mL). The aqueous layer was separated, basified to pH 9, and extracted with EtOAc (200 mL×2). The combined organic layers were washed brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give (S)-3-amino-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl isoquinolin-3-ylcarbamate (2.7 g) as a light yellow foam solid, which was used without further purification. LRMS (M+H+) m/z 460.1.

Workup

  1. customquenched with MeOH (20.0 mL)
  2. stirringThe resulting mixture was stirred for another 15 min
  3. concentrationconcentrated to dryness
  4. custompartitioned in between ether (30 mL) and HCl (2 N, 20 mL)
  5. customThe aqueous layer was separated
  6. extractionextracted with EtOAc (200 mL×2)
  7. washThe combined organic layers were washed brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0d4554bf587149e386516367c7abc395
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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