Isobutylamine → {(1S,2S,4S)-4-Isobutylcarbamoyl-1-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester

HRID 1694949Notes

Reaction equation

HRID 1694949 reaction equation
[CH2:1]([NH2:5])[CH:2]([CH3:4])[CH3:3].OC1C=CC=CN=1.[C:13]([O:17][C:18](=[O:48])[NH:19][C@H:20]([C@@H:39]1[CH2:43][C@@H:42]([CH:44]([CH3:46])[CH3:45])[C:41](=[O:47])[O:40]1)[CH2:21][N:22]1[CH2:27][C:26](=[O:28])[N:25]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[CH3:36])[CH2:24][C:23]1([CH3:38])[CH3:37])([CH3:16])([CH3:15])[CH3:14]>O>[C:13]([O:17][C:18](=[O:48])[NH:19][C@@H:20]([CH2:21][N:22]1[CH2:27][C:26](=[O:28])[N:25]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[CH3:36])[CH2:24][C:23]1([CH3:38])[CH3:37])[C@@H:39]([OH:40])[CH2:43][C@H:42]([C:41](=[O:47])[NH:5][CH2:1][CH:2]([CH3:4])[CH3:3])[CH:44]([CH3:46])[CH3:45])([CH3:14])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 6558IsobutylamineHCID 66645725{(S)-2-[2,2-Dimethyl-4-(5-fluoro-2-methylphenyl)-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 66645880{(1S,2S,4S)-4-Isobutylcarbamoyl-1-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl esterYield 100.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

0.4 ml of isobutylamine (3.96 mmol) and 8 mg of 2-hydroxypyridine (0.079 mmol) were added to 200 mg of {(S)-2-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (70f) (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/methanol=20/1) to obtain 226 mg of the title compound (yield: 99%).

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/methanol=20/1)

Sources & evidence

ORD record
ord-c153931bd8654bbf88ecc8f8d8a71631
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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