Ammonia → (r)-3-((s)-2-(4,4-Dimethyl-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2,5-dioxoimidazolidin-1-yl)-2-(cyclopropylmethyl)acetylamino)-3-methylpropionamide

HRID 1840616Notes

Reaction equation

HRID 1840616 reaction equation
C1CCC([N:7]=C=NC2CCCCC2)CC1.[CH3:16][C:17]1([CH3:58])[C:21](=[O:22])[N:20]([C@@H:23]([CH2:33][CH:34]2[CH2:36][CH2:35]2)[C:24]([NH:26][C@H:27]([CH3:32])[CH2:28][C:29]([OH:31])=O)=[O:25])[C:19](=[O:37])[N:18]1[CH2:38][C:39]1[CH:44]=[CH:43][C:42]([NH:45][C:46]([NH:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[CH3:55])=[O:47])=[C:41]([O:56][CH3:57])[CH:40]=1.C1C=CC2N(O)N=NC=2C=1.N>CN(C=O)C>[CH3:58][C:17]1([CH3:16])[C:21](=[O:22])[N:20]([C@@H:23]([CH2:33][CH:34]2[CH2:35][CH2:36]2)[C:24]([NH:26][C@H:27]([CH3:32])[CH2:28][C:29]([NH2:7])=[O:31])=[O:25])[C:19](=[O:37])[N:18]1[CH2:38][C:39]1[CH:44]=[CH:43][C:42]([NH:45][C:46]([NH:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[CH3:55])=[O:47])=[C:41]([O:56][CH3:57])[CH:40]=1

Participants

6

Reactant 4

HCID 222Ammonia2×HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 9960205(r)-3-((s)-2-(4,4-Dimethyl-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2,5-dioxoimidazolidin-1-yl)-2-(cyclopropylmethyl)acetylamino)-3-methylpropionic acid

Product 1

HCID 12044587(r)-3-((s)-2-(4,4-Dimethyl-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2,5-dioxoimidazolidin-1-yl)-2-(cyclopropylmethyl)acetylamino)-3-methylpropionamideYield 82.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

131 mg (0.636 mmol) of DCC were added to a solution of 330 mg (0.555 mmol) of the compound of Example 1 and 125 mg (0.926 mmol) of HOBT in 4 mL of absolute DMF, the mixture was stirred at room temperature for 1 hour and then 47 μL (0.555 mmol) of a 25% strength aqueous ammonia solution were added. The mixture was allowed to stand overnight at room temperature, a further 16 μL of a 25% strength aqueous ammonia solution were added and the mixture was stirred for 4 hours. After filtration, the filtrate was concentrated in vacuo, the residue was dissolved in ethyl acetate and the ethyl acetate phase was washed twice in each case with an aqueous KHSO4/K2SO4 solution, a saturated NaHCO3 solution and water. After drying the organic phase over sodium sulfate and filtering, the solvent was removed in vacuo and the residue was chromatographed over silica gel using ethyl acetate. After concentrating the product fractions and freeze drying, 272 mg (82%) of the title compound were obtained.

Workup

  1. waitto stand overnight at room temperature
  2. stirringthe mixture was stirred for 4 hours
  3. filtrationAfter filtration
  4. concentrationthe filtrate was concentrated in vacuo
  5. dissolutionthe residue was dissolved in ethyl acetate
  6. washthe ethyl acetate phase was washed twice in each case with an aqueous KHSO4/K2SO4 solution
  7. dry with materialAfter drying the organic phase over sodium sulfate
  8. filtrationfiltering
  9. customthe solvent was removed in vacuo
  10. customthe residue was chromatographed over silica gel
  11. concentrationAfter concentrating the product fractions and freeze
  12. customdrying

Sources & evidence

ORD record
ord-05e989c270324dd98c6ae0c8d8aa9d1c
Source dataset
uspto-grants-2004_01
Patent number
US06680333B2

Reaction notes

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