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

HRID 1695003Notes

Reaction equation

HRID 1695003 reaction equation
OC1C=CC=CN=1.[C:8]([O:12][C:13](=[O:41])[NH:14][C@H:15]([C@@H:33]1[CH2:37][C@@H:36]([CH2:38][CH3:39])[C:35](=[O:40])[O:34]1)[CH2:16][N:17]1[CH2:22][C:21](=[O:23])[N:20]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH3:30])[CH2:19][C:18]1([CH3:32])[CH3:31])([CH3:11])([CH3:10])[CH3:9].[CH3:42][C:43]([CH3:47])([CH3:46])[CH2:44][NH2:45]>>[C:8]([O:12][C:13](=[O:41])[NH:14][C@@H:15]([CH2:16][N:17]1[CH2:22][C:21](=[O:23])[N:20]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH3:30])[CH2:19][C:18]1([CH3:31])[CH3:32])[C@@H:33]([OH:34])[CH2:37][C@H:36]([C:35](=[O:40])[NH:45][CH2:44][C:43]([CH3:47])([CH3:46])[CH3:42])[CH2:38][CH3:39])([CH3:11])([CH3:10])[CH3:9]

Participants

4

Reactant 3

HCID 79882NeopentylamineHCID 66645525{(S)-2-[2,2-Dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterHCID 178516071HCID 178516071, compound

Product 1

HCID 66645545{(1S,2S,4R)-4-(2,2-Dimethylpropylcarbamoyl)-1-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxyhexyl}carbamic acid t-butyl esterYield 89%

Conditions

Temperature
80 °C

Procedure

10 mg of 2-hydroxypyridine (0.11 mmol) was added to a solution of 100 mg of {(S)-2-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (110b) (0.21 mmol) in (2,2-dimethylpropyl)amine (0.5 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 ethyl acetate. 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:ethyl acetate) to obtain 105 mg of the title compound (yield: 89%).

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 ethyl acetate
  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:ethyl acetate)

Sources & evidence

ORD record
ord-f038d60f04774f3a9188168f3be58be3
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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