3-Amino-2,2-dimethylpropanamide → {(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

HRID 1694912Notes

Reaction equation

HRID 1694912 reaction equation
[NH2:1][CH2:2][C:3]([CH3:8])([CH3:7])[C:4]([NH2:6])=[O:5].OC1C=CC=CN=1.[CH2:16]([O:23][C:24](=[O:56])[NH:25][C@H:26]([C@@H:47]1[CH2:51][C@@H:50]([CH:52]([CH3:54])[CH3:53])[C:49](=[O:55])[O:48]1)[CH2:27][N:28]1[CH2:33][C:32](=[O:34])[N:31]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[O:41][CH2:42][O:43][CH3:44])[CH2:30][C:29]1([CH3:46])[CH3:45])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(N(CC)CC)C>[CH2:16]([O:23][C:24](=[O:56])[NH:25][C@@H:26]([CH2:27][N:28]1[CH2:33][C:32](=[O:34])[N:31]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[O:41][CH2:42][O:43][CH3:44])[CH2:30][C:29]1([CH3:45])[CH3:46])[C@@H:47]([OH:48])[CH2:51][C@H:50]([C:49](=[O:55])[NH:1][CH2:2][C:3]([C:4](=[O:5])[NH2:6])([CH3:8])[CH3:7])[CH:52]([CH3:53])[CH3:54])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 111593153-Amino-2,2-dimethylpropanamideHCID 66645611HCID 66645611, compoundHCID 178516071HCID 178516071, compound

Product 1

HCID 66645737{(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 esterYield 52.4%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

161 mg of 3-amino-2,2-di(methyl)propionamide obtained in Reference Example 2 (1.39 mmol) and 44 mg of 2-hydroxypyridine (0.46 mmol) were added to a solution of 263 mg of {(S)-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]-2-[4-(2-methoxymethoxyphenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]ethyl}carbamic acid benzyl ester obtained in the above reaction (0.46 mmol) in triethylamine (4.6 ml), and the mixture was stirred at 80° C. for two hours. The reaction mixture was cooled and then concentrated under reduced pressure and further stirred at 80° C. for 9 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. The residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=40/3) to obtain 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 (yield: 52%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. stirringfurther stirred at 80° C. for 9 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-8afa2877d1ed4ae99629a0efb9497be9
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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