1,2-Dichloroethane → (S)-2-{[(R)-5-(4-bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-propionic acid tert-butyl ester

HRID 1040536Notes

Reaction equation

HRID 1040536 reaction equation
[Br:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][C@@:7]2([CH3:27])[N:11]3[C:12]([C:15]([OH:17])=O)=[CH:13][N:14]=[C:10]3[N:9]([C:18]3[CH:23]=[C:22]([Cl:24])[CH:21]=[C:20]([Cl:25])[CH:19]=3)[C:8]2=[O:26])=[CH:4][CH:3]=1.Cl.[C:31]([O:35][C:36](=[O:40])[C@@H:37]([NH2:39])[CH3:38])([CH3:34])([CH3:33])[CH3:32].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[C:31]([O:35][C:36](=[O:40])[C@@H:37]([NH:39][C:15]([C:12]1[N:11]2[C@@:7]([CH2:6][C:5]3[CH:28]=[CH:29][C:2]([Br:1])=[CH:3][CH:4]=3)([CH3:27])[C:8](=[O:26])[N:9]([C:18]3[CH:19]=[C:20]([Cl:25])[CH:21]=[C:22]([Cl:24])[CH:23]=3)[C:10]2=[N:14][CH:13]=1)=[O:17])[CH3:38])([CH3:34])([CH3:33])[CH3:32]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 11275390tert-Butyl alaninate hydrochlorideHCID 58431129(R)-5-(4-bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid

Product 1

HCID 58430923(S)-2-{[(R)-5-(4-bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-propionic acid tert-butyl esterYield 80.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (R)-5-(4-bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid (2.5 g, 5.0 mmol) in DMF (5 mL) was added (S)-2-amino-propionic acid tert-butyl ester hydrochloride (0.92 g, 5.0 mmol), HOBt (0.68 g, 5.0 mmol), EDC (0.97 g, 5.0 mmol) and DMAP (0.061 g, 0.50 mmol). The reaction mixture was heated at 80° C. for 12 h. The mixture was allowed to cool to room temperature and diluted with water (100 mL). The mixture was extracted with EtOAc (3×100 mL) and the combined organic layers were washed with water, brine and dried with MgSO4. The mixture was filtered and concentrated in vacuo to give 2.5 g of (S)-2-{[(R)-5-(4-bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-propionic acid tert-butyl ester as a yellow solid, m/z 623.5 [M+1]+.

Workup

  1. temperatureto cool to room temperature
  2. extractionThe mixture was extracted with EtOAc (3×100 mL)
  3. washthe combined organic layers were washed with water, brine
  4. dry with materialdried with MgSO4
  5. filtrationThe mixture was filtered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7b5427c9814c4a008923063a8592e079
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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