Morpholine → 1-{[(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}-cyclopropanecarboxylic acid

HRID 2038810Notes

Reaction equation

HRID 2038810 reaction equation
C([O:4][C:5]([C:7]1([NH:10][C:11]([C:13]2[N:17]3[C@@:18]([CH2:31][C:32]4[CH:37]=[CH:36][C:35]([Br:38])=[CH:34][CH:33]=4)([CH3:30])[C:19](=[O:29])[N:20]([C:21]4[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=4)[C:16]3=[N:15][CH:14]=2)=[O:12])[CH2:9][CH2:8]1)=[O:6])C=C.N1CCOCC1>C1COCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:38][C:35]1[CH:36]=[CH:37][C:32]([CH2:31][C@@:18]2([CH3:30])[N:17]3[C:13]([C:11]([NH:10][C:7]4([C:5]([OH:6])=[O:4])[CH2:8][CH2:9]4)=[O:12])=[CH:14][N:15]=[C:16]3[N:20]([C:21]3[CH:22]=[C:23]([Cl:28])[CH:24]=[C:25]([Cl:27])[CH:26]=3)[C:19]2=[O:29])=[CH:33][CH:34]=1

Participants

6

Reactant 2

HCID 8083MorpholineHCID 584310001-{[(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}-cyclopropanecarboxylic acid allyl ester

Product 1

HCID 584311161-{[(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}-cyclopropanecarboxylic acid

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-{[(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}-cyclopropanecarboxylic acid allyl ester (200 mg, 0.32 mmol) and morpholine (0.282 mL, 3.24 mmol) in 2 mL of THF was added Pd(Ph3P)4 (19 mg, 0.016 mmol). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was then diluted with 30 mL of EtOAc and washed with 10 mL each of 10% HCl solution, water, and brine, dried over Na2SO4, filtered, and concentrated. The residue was applied to a SiliaBond Carbonate preloaded cartridge (2 g, 0.7 mmol/g, Silicycle). The column was eluted with 30 mL of 10% MeOH in CH2Cl2 followed by 200 mL of 0.1:1:9 TFA/MeOH/CH2Cl2 to furnish 142 mg 76%) of the title compound as a colorless foam, m/z 579.4 [M+1]+.

Workup

  1. washwashed with 10 mL each of 10% HCl solution, water, and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. washThe column was eluted with 30 mL of 10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-b279f7ec1ca44dcda203406b5f6c01e6
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

Loading…