1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Tert-butyl(1r)-2,2-dimethyl-1-((4-((5-methyl-3-oxo-1h-imidazo[1,5-c]imidazol-2(3h)-yl)methyl)-1-piperidinyl)carbonyl)propylcarbamate

HRID 1162329Notes

Reaction equation

HRID 1162329 reaction equation
[C:1]([NH:8][C@@H:9]([C:14]([OH:16])=O)[C:10]([CH3:13])([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH3:40][C:41]1[N:45]2[C:46](=[O:56])[N:47]([CH2:49][CH:50]3[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]3)[CH2:48][C:44]2=[CH:43][N:42]=1.C1CCN2C(=NCCC2)CC1>C(#N)C.C(N(CC)CC)C>[CH3:13][C:10]([CH3:11])([CH3:12])[C@@H:9]([NH:8][C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7])[C:14]([N:53]1[CH2:54][CH2:55][CH:50]([CH2:49][N:47]2[CH2:48][C:44]3=[CH:43][N:42]=[C:41]([CH3:40])[N:45]3[C:46]2=[O:56])[CH2:51][CH2:52]1)=[O:16]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 7005057(2R)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acidHCID 231381375-methyl-2-(4-piperidinyl)methyl-1,2-dihydro-3H-imidazo[1,5-c]imidazol-3-one dihydrochloride

Product 1

HCID 91133213Tert-butyl(1r)-2,2-dimethyl-1-((4-((5-methyl-3-oxo-1h-imidazo[1,5-c]imidazol-2(3h)-yl)methyl)-1-piperidinyl)carbonyl)propylcarbamateYield 90.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of Boc-D-tert-leucine (0.69 g), HOBt (0.69 g) and WSC (0.86 g) in acetonitrile (20 ml) was added a solution of 5-methyl-2-(4-piperidinylmethyl)-1,2-dihydro-3H-imidazo[1,5-c]imidazol-3-one dihydrochloride (0.91 g) as described above, DBU (0.6 ml) and triethylamine (0.61 ml) in acetonitrile (20 ml), and mixed for 15 hours. The solvent was distilled off under reduced pressure, and the residue was dissolved in dichloromethane. The dichloromethane solution was washed with an aqueous sodium hydrogen carbonate solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified with basic silica gel column (ethyl acetate/methanol=10/1) to obtain the title compound as colorless powder (1.2 g, 66%).

Workup

  1. additionmixed for 15 hours
  2. distillationThe solvent was distilled off under reduced pressure
  3. dissolutionthe residue was dissolved in dichloromethane
  4. washThe dichloromethane solution was washed with an aqueous sodium hydrogen carbonate solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was purified with basic silica gel column (ethyl acetate/methanol=10/1)

Sources & evidence

ORD record
ord-6a82fc3ea4064785ba3fd6ad8fdb3702
Source dataset
uspto-grants-2010_10
Patent number
US07820673B2

Reaction notes

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