Diphosgene → HCID 58615465, compound

HRID 2222993Notes

Reaction equation

HRID 2222993 reaction equation
[O:1]=[C:2](Cl)OC(Cl)(Cl)Cl.[NH2:9][CH:10]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:11]([NH:13][C@@H:14]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:15]([NH:17][C:18]1[S:19][CH:20]=[C:21]([C:23]([NH2:25])=[O:24])[N:22]=1)=[O:16])=[O:12].C(N(C(C)C)CC)(C)C>CO.C1(C)C=CC=CC=1.ClCCl>[O:1]=[C:2]1[NH:9][CH:10]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:11](=[O:12])[N:13]1[C@@H:14]([CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:15]([NH:17][C:18]1[S:19][CH:20]=[C:21]([C:23]([NH2:25])=[O:24])[N:22]=1)=[O:16]

Participants

7

Reactant 3

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 86604060HCID 86604060, compound

Product 1

HCID 58615465HCID 58615465, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of diphosgene (3.7 μL, 0.03 mmol) in a 1:1 v/v mixture of dichloromethane and toluene (0.5 mL total volume) was added dropwise with stirring a solution of 2-[2-(S)-(2-amino-2-phenyl-acetylamino)-3-phenyl-propionylamino]-thiazole-4-carboxylic acid amide (21.5 mg, 0.051 mmol) and diisopropylethylamine (24 μL, 0.14 mmol) in a 1:1 v/v mixture of dichloromethane and toluene (1 mL total volume). After stirring for 30 minutes, methanol (0.1 mL) was added and the reaction mixture concentrated in vacuo. The residue was purified by reverse phase high performance liquid chromatography using a C-18 stationary phase gradient eluted with a water/acetonitrile mixture containing 0.1% v/v trifluoroacetic acid in both components of the solvent system. After lyophilization 2-[(S)-2-(2,5-dioxo-4-phenyl-imidazolidin-1-yl)-3-phenyl-propionylamino]-thiazole-4-carboxylic acid amide was obtained as an amorphous colorless solid (4.0 mg, 18%).

Workup

  1. additionwas added dropwise
  2. concentrationthe reaction mixture concentrated in vacuo
  3. customThe residue was purified by reverse phase high performance liquid chromatography
  4. washeluted with a water/acetonitrile mixture
  5. additioncontaining 0.1% v/v trifluoroacetic acid in both components of the solvent system

Sources & evidence

ORD record
ord-7f0efffdb72c4c4287c2ba17683815b2
Source dataset
uspto-grants-2008_05
Patent number
US07371869B2

Reaction notes

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