2-Methylbutylamine, (S)- → {(1S,2S,4S)-1-[4-(2-Chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methyl-4-[(S)-2-methylbutylcarbamoyl]hexyl}carbamic acid t-butyl ester

HRID 1694897Notes

Reaction equation

HRID 1694897 reaction equation
[CH3:1][C@@H:2]([CH2:5][CH3:6])[CH2:3][NH2:4].OC1C=CC=CN=1.[C:14]([O:18][C:19](=[O:48])[NH:20][C@H:21]([C@@H:39]1[CH2:43][C@@H:42]([CH:44]([CH3:46])[CH3:45])[C:41](=[O:47])[O:40]1)[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[Cl:36])[CH2:25][C:24]1([CH3:38])[CH3:37])([CH3:17])([CH3:16])[CH3:15]>O>[C:14]([O:18][C:19](=[O:48])[NH:20][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[Cl:36])[CH2:25][C:24]1([CH3:38])[CH3:37])[C@@H:39]([OH:40])[CH2:43][C@H:42]([C:41](=[O:47])[NH:4][CH2:3][C@@H:2]([CH3:1])[CH2:5][CH3:6])[CH:44]([CH3:46])[CH3:45])([CH3:15])([CH3:17])[CH3:16]

Participants

5

Reactant 3

HCID 27242722-Methylbutylamine, (S)-HCID 66645421{(S)-2-[4-(2-Chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterHCID 178516071HCID 178516071, compound

Product 1

HCID 66645798{(1S,2S,4S)-1-[4-(2-Chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methyl-4-[(S)-2-methylbutylcarbamoyl]hexyl}carbamic acid t-butyl esterYield 79.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

0.24 ml of (S)-2-methylbutylamine (2.0 mmol) and 37 mg of 2-hydroxypyridine (0.39 mmol) were added to 200 mg of {(S)-2-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (1m) (0.39 mmol), and the mixture was stirred at 80° C. for four hours. The reaction mixture was cooled and then water was added, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine and then dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/acetone=3/1) to obtain 184 mg of the title compound (yield: 79%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionfollowed by extraction with ethyl acetate
  3. washThen, the organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. customthe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/acetone=3/1)

Sources & evidence

ORD record
ord-29c53817b8934c7dbbf7d357b1e4b05a
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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