Fumaric Acid → (2S,4S,5S)-5-Amino-4-hydroxy-2-isopropyl-6-[4-(2-methoxymethoxyphenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]hexanoic acid (2-carbamoyl-2-methylpropyl)amide hemifumarate

HRID 1694913Notes

Reaction equation

HRID 1694913 reaction equation
[H][H].[C:3]([OH:10])(=[O:9])/[CH:4]=[CH:5]/[C:6]([OH:8])=[O:7].[C:11]([C:14]([CH3:49])([CH3:48])[CH2:15][NH:16][C:17](=[O:47])[C@H:18]([CH:44]([CH3:46])[CH3:45])[CH2:19][C@H:20]([OH:43])[C@@H:21]([NH2:42])[CH2:22][N:23]1[CH2:28][C:27](=[O:29])[N:26]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[O:36][CH2:37][O:38][CH3:39])[CH2:25][C:24]1([CH3:41])[CH3:40])(=[O:13])[NH2:12]>CO>[C:3]([OH:10])(=[O:9])/[CH:4]=[CH:5]/[C:6]([OH:8])=[O:7].[C:11]([C:14]([CH3:48])([CH3:49])[CH2:15][NH:16][C:17](=[O:47])[C@H:18]([CH:44]([CH3:45])[CH3:46])[CH2:19][C@H:20]([OH:43])[C@@H:21]([NH2:42])[CH2:22][N:23]1[CH2:28][C:27](=[O:29])[N:26]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[O:36][CH2:37][O:38][CH3:39])[CH2:25][C:24]1([CH3:40])[CH3:41])(=[O:13])[NH2:12].[NH2:42][C@@H:21]([CH2:22][N:23]1[CH2:28][C:27](=[O:29])[N:26]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[O:36][CH2:37][O:38][CH3:39])[CH2:25][C:24]1([CH3:41])[CH3:40])[C@@H:20]([OH:43])[CH2:19][C@@H:18]([CH:44]([CH3:46])[CH3:45])[C:17]([NH:16][CH2:15][C:14]([CH3:48])([C:11](=[O:13])[NH2:12])[CH3:49])=[O:47]

Participants

5

Reactant 3

HCID 444972Fumaric AcidHCID 66645361(2s,4s,5s)-5-Amino-4-hydroxy-2-isopropyl-6-[4-(2-methoxymethoxyphenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]hexanoic acid (2-carbamoyl-2-methylpropyl)amideHCID 178418361HCID 178418361, compound

Product 1

HCID 131729636(2S,4S,5S)-5-Amino-4-hydroxy-2-isopropyl-6-[4-(2-methoxymethoxyphenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]hexanoic acid (2-carbamoyl-2-methylpropyl)amide hemifumarateYield 87.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of 166 mg of {(1S,2S,4S)-4-(2-carbamoyl-2-methylpropylcarbamoyl)-2-hydroxy-1-[4-(2-methoxymethoxyphenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-5-methylhexyl}carbamic acid benzyl ester obtained in the above reaction (0.24 mmol) and 83 mg of 10% palladium-carbon (50% wet) in ethanol (3 ml) was stirred under a hydrogen atmosphere at room temperature for two hours. Hydrogen in the reaction vessel was replaced by nitrogen. Then, palladium-carbon was separated by filtration and washed with ethanol. The solvent was evaporated from the filtrate under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol/triethylamine=200/20/1). 10.8 mg of fumaric acid (0.093 mmol) was added to a solution of 102 mg of (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-6-[4-(2-methoxymethoxyphenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]hexanoic acid (2-carbamoyl-2-methylpropyl)amide obtained above (0.18 mmol) in methanol (3 ml), and the mixture was stirred at room temperature for five minutes. The solvent was evaporated under reduced pressure to obtain 99 mg of the title compound (yield: 66%).

Workup

  1. customThen, palladium-carbon was separated by filtration
  2. washwashed with ethanol
  3. customThe solvent was evaporated from the filtrate under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol/triethylamine=200/20/1)
  5. stirringthe mixture was stirred at room temperature for five minutes
  6. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-dc522e78ed8d445d8f10b1ba5b89453b
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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