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

HRID 1694947Notes

Reaction equation

HRID 1694947 reaction equation
[CH3:1][C:2]([CH3:6])([CH3:5])[CH2:3][NH2:4].OC1C=CC=CN=1.[C:14]([O:18][C:19](=[O:49])[NH:20][C@H:21]([C@@H:40]1[CH2:44][C@@H:43]([CH:45]([CH3:47])[CH3:46])[C:42](=[O:48])[O:41]1)[CH2:22][N:23]1[CH2:28][C:27](=[O:29])[N:26]([C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=2[CH3:37])[CH2:25][C:24]1([CH3:39])[CH3:38])([CH3:17])([CH3:16])[CH3:15]>O>[C:14]([O:18][C:19](=[O:49])[NH:20][C@@H:21]([CH2:22][N:23]1[CH2:28][C:27](=[O:29])[N:26]([C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=2[CH3:37])[CH2:25][C:24]1([CH3:38])[CH3:39])[C@@H:40]([OH:41])[CH2:44][C@H:43]([C:42](=[O:48])[NH:4][CH2:3][C:2]([CH3:6])([CH3:5])[CH3:1])[CH:45]([CH3:47])[CH3:46])([CH3:15])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 79882NeopentylamineHCID 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 66645581{(1S,2S,4S)-4-(2,2-Dimethylpropylcarbamoyl)-1-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

0.94 ml of (2,2-dimethylpropyl)amine (8.0 mmol) and 7.6 mg of 2-hydroxypyridine (0.08 mmol) were added to 202 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) (0.4 mmol), and the mixture was stirred at 70° 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 177 mg of the title compound (yield: 75%).

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-c8230539d75b42739923d2014dcd4f7d
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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