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

HRID 1040558Notes

Reaction equation

HRID 1040558 reaction equation
[C:1]([C:3]1[CH:36]=[CH:35][C:6]([CH2:7][C@@:8]2([CH3:34])[N:12]3[C:13]([C:16]([NH:18][C:19]4([C:22]([OH:24])=O)[CH2:21][CH2:20]4)=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=3)[C:9]2=[O:33])=[CH:5][CH:4]=1)#[N:2].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(CC)CC.[C:58]([O:62][C:63]([NH:65][NH:66][C:67]([C:69]1([NH2:72])[CH2:71][CH2:70]1)=[O:68])=[O:64])([CH3:61])([CH3:60])[CH3:59]>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[C:58]([O:62][C:63]([NH:65][NH:66][C:67]([C:69]1([NH:72][C:22]([C:19]2([NH:18][C:16]([C:13]3[N:12]4[C@@:8]([CH2:7][C:6]5[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:36][CH:35]=5)([CH3:34])[C:9](=[O:33])[N:10]([C:25]5[CH:26]=[C:27]([Cl:32])[CH:28]=[C:29]([Cl:31])[CH:30]=5)[C:11]4=[N:15][CH:14]=3)=[O:17])[CH2:20][CH2:21]2)=[O:24])[CH2:71][CH2:70]1)=[O:68])=[O:64])([CH3:61])([CH3:59])[CH3:60]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 584309681-{[(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acidHCID 67390113N'-(1-amino-cyclopropanecarbonyl)-hydrazinecarboxylic acid tert-butyl ester

Product 1

HCID 58430863N'-{1-[(1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarbonyl)-amino]-cyclopropanecarbonyl}-hydrazinecarboxylic acid tert-butyl esterYield 96%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid (0.25 g, 0.48 mmol) in DMF (2 mL) was added HOAt (0.065 g, 0.48 mmol), EDC (0.092 g, 0.48 mmol), DMAP (0.005 g, 0.041 mmol), Et3N (0.066 mL, 0.48 mmol). The reaction allowed to stir for 10 min at room temperature. To this mixture was added N′-(1-amino-cyclopropanecarbonyl)-hydrazinecarboxylic acid tert-butyl ester (0.10 g, 0.48 mmol) and the reaction was heated at 70° C. for 15 h. The mixture was cooled to room temperature, diluted with water and extracted with EtOAc (3×50 mL). The combined extracts were washed with saturated NaHCO3, 2N HCl, brine and dried with MgSO4. The mixture was filtered and concentrated in vacuo to give N′-{1-[(1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarbonyl)-amino]-cyclopropanecarbonyl}-hydrazinecarboxylic acid tert-butyl ester (0.33 g, 96%) as a yellow solid, m/z 721.9 [M+1]+.

Workup

  1. temperaturethe reaction was heated at 70° C. for 15 h
  2. temperatureThe mixture was cooled to room temperature
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined extracts were washed with saturated NaHCO3, 2N HCl, brine
  5. dry with materialdried with MgSO4
  6. filtrationThe mixture was filtered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-68e211e9d2c643ae9c011aeab7a535c2
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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