Sodium Carbonate → (R)-5-[4-(2-Hydroxy-ethoxy)-phenyl]-3-[(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-methyl-propyl]-imidazolidine-2,4-dione

HRID 227154Notes

Reaction equation

HRID 227154 reaction equation
C(O[C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])(C)(C)C.IC1C=C(N)C(N)=CC=1.C(N(C(C)C)CC)(C)C.N1([O:43][C:44](N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(=O)([O-])[O-].[Na+].[Na+].C(OC(=O)[NH:63][C@H:64]([C:68](=O)[NH:69][C:70]1[CH:75]=[CH:74][C:73]([I:76])=[CH:72][C:71]=1[NH2:77])[CH:65]([CH3:67])[CH3:66])(C)(C)C.[C:80]([O:84][C:85](=O)N[C@H](C(=O)NC1C=C(I)C=CC=1N)C(C)C)([CH3:83])([CH3:82])C>CN(C)C=O>[OH:43][CH2:44][CH2:85][O:84][C:80]1[CH:82]=[CH:14][C:13]([C@H:9]2[NH:8][C:6](=[O:7])[N:63]([C@H:64]([C:68]3[NH:69][C:70]4[CH:75]=[CH:74][C:73]([I:76])=[CH:72][C:71]=4[N:77]=3)[CH:65]([CH3:66])[CH3:67])[C:10]2=[O:12])=[CH:15][CH:83]=1

Participants

9

Reactant 7

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 130500O-benzotriazol-1-yl-tetramethyluroniumHCID 112070494-Iodobenzene-1,2-diamineHCID 66815259[(S)-1-(2-amino-5-iodo-phenylcarbamoyl)-2-methyl-propyl]-carbamic acid tert-butyl esterHCID 66815284[(S)-1-(2-amino-4-iodo-phenylcarbamoyl)-2-methyl-propyl]-carbamic acid tert-butyl ester

Product 1

HCID 178448265(R)-5-[4-(2-Hydroxy-ethoxy)-phenyl]-3-[(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-methyl-propyl]-imidazolidine-2,4-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To the solution of (S)-2-tert-butoxycarbonylamino-3-methyl-butyric acid (0.33 g, 1.5 mmol), 4-iodo-benzene-1,2-diamine (0.35 g, 1.5 mmol) and diisopropylethyl amine (0.8 mL, 4.5 mmol) in N,N-dimethylformamide (6 mL) was added dropwise a solution of O-benzotriazol-1-yl-N,N, N′,N′-tetramethyluronium hexaflurorophosphate (0.71 g, 1.75 mmol) N,N-dimethylformamide (2 mL). The reaction mixture was stirred for 12 hours at room temperature. After adding aqueous sodium carbonate solution, the reaction mixture was extracted with ethyl acetate and the organic layer was washed with aqueous sodium carbonate solution and brine, dried over sodium sulfate, filtered, and concentrated to give a mixture of regioisomers, [(S)-1-(2-amino-4-iodo-phenylcarbamoyl)-2-methyl-propyl]-carbamic acid tert-butyl ester and [(S)-1-(2-amino-5-iodo-phenylcarbamoyl)-2-methyl-propyl]-carbamic acid tert-butyl ester (0.65 g, 100%).

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. washthe organic layer was washed with aqueous sodium carbonate solution and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give

Sources & evidence

ORD record
ord-6a93aaf95e7e43888a36af294f31d324
Source dataset
uspto-grants-2009_07
Patent number
US07557221B2

Reaction notes

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