Triethylamine → 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 tert-butyl ester

HRID 1040521Notes

Reaction equation

HRID 1040521 reaction equation
[C:1]([C:3]1[CH:30]=[CH:29][C:6]([CH2:7][C@@:8]2([CH3:28])[N:12]3[C:13]([C:16](O)=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:19]3[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=3)[C:9]2=[O:27])=[CH:5][CH:4]=1)#[N:2].[C:31]([O:35][C:36]([C:38]1([NH2:41])[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>CN(C=O)C>[C:31]([O:35][C:36]([C:38]1([NH:41][C:16]([C:13]2[N:12]3[C@@:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:30][CH:29]=4)([CH3:28])[C:9](=[O:27])[N:10]([C:19]4[CH:20]=[C:21]([Cl:26])[CH:22]=[C:23]([Cl:25])[CH:24]=4)[C:11]3=[N:15][CH:14]=2)=[O:17])[CH2:39][CH2:40]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57671084Tert-butyl 1-aminocyclopropanecarboxylateHCID 58430912(R)-5-(4-Cyano-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 584312301-{[(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 tert-butyl esterYield 87.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid (3.3 g, 7.48 mmol), 1-amino-cyclopropane-carboxylic acid tert-butyl ester (1.8 g, 11.4 mmol) and HATU (4.27 g, 11.2 mmol) were dissolved in anhydrous DMF (20 mL). The mixture was stirred for 15 min. Et3N (2.95 mL, 20.4 mmol) was then added to the reaction. After 30 min, the crude reaction was concentrated in vacuo. The residue was purified by flash chromatography on silica gel (10% to 30% EtOAc/Hexanes) to give 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 tert-butyl ester (3.8 g, 6.55 mmol, 87.5%) as a white solid, m/z 580.5 [M+1]+.

Workup

  1. waitAfter 30 min
  2. customthe crude reaction
  3. concentrationwas concentrated in vacuo
  4. customThe residue was purified by flash chromatography on silica gel (10% to 30% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-c154c6f6df784dec8610255eb63a4acd
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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