3-Amino-2,2-dimethylpropanamide → {(1S,2S,4S)-4-(2-Carbamoyl-2-methylpropylcarbamoyl)-1-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester

HRID 1694895Notes

Reaction equation

HRID 1694895 reaction equation
[NH2:1][CH2:2][C:3]([CH3:8])([CH3:7])[C:4]([NH2:6])=[O:5].OC1C=CC=CN=1.[C:16]([O:20][C:21](=[O:50])[NH:22][C@H:23]([C@@H:41]1[CH2:45][C@@H:44]([CH:46]([CH3:48])[CH3:47])[C:43](=[O:49])[O:42]1)[CH2:24][N:25]1[CH2:30][C:29](=[O:31])[N:28]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[Cl:38])[CH2:27][C:26]1([CH3:40])[CH3:39])([CH3:19])([CH3:18])[CH3:17]>C(N(CC)CC)C>[C:16]([O:20][C:21](=[O:50])[NH:22][C@@H:23]([CH2:24][N:25]1[CH2:30][C:29](=[O:31])[N:28]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[Cl:38])[CH2:27][C:26]1([CH3:39])[CH3:40])[C@@H:41]([OH:42])[CH2:45][C@H:44]([C:43](=[O:49])[NH:1][CH2:2][C:3]([C:4](=[O:5])[NH2:6])([CH3:8])[CH3:7])[CH:46]([CH3:48])[CH3:47])([CH3:17])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 111593153-Amino-2,2-dimethylpropanamideHCID 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 66645450{(1S,2S,4S)-4-(2-Carbamoyl-2-methylpropylcarbamoyl)-1-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl esterYield 66.9%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

140 mg of 3-amino-2,2-di(methyl)propionamide obtained in Reference Example 2 (1.21 mmol) and 38 mg of 2-hydroxypyridine (0.40 mmol) were added to a solution of 205 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) (0.40 mmol) in triethylamine (4 ml), and the mixture was stirred at 80° C. for four hours. The reaction mixture was cooled and then concentrated under reduced pressure and further stirred at 80° C. for 14 hours. The reaction mixture was cooled and then water was added, followed by extraction with methylene chloride. Then, the organic layer was dried over anhydrous magnesium 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=40/3) to obtain 167 mg of the title compound (yield: 66%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. stirringfurther stirred at 80° C. for 14 hours
  4. temperatureThe reaction mixture was cooled
  5. additionwater was added
  6. extractionfollowed by extraction with methylene chloride
  7. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
  8. filtrationAfter filtration
  9. customthe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (elution solvent: methylene chloride/methanol=40/3)

Sources & evidence

ORD record
ord-b87bd1c3f4254bfaa2dab21a7cc04493
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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