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

HRID 1694965Notes

Reaction equation

HRID 1694965 reaction equation
OC1C=CC=CN=1.[C:8]([O:12][C:13](=[O:40])[NH:14][C@H:15]([C@@H:33]1[CH2:37][C@@H:36]([CH3:38])[C:35](=[O:39])[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].O.[CH3:42][C:43]([CH3:47])([CH3:46])[CH2:44][NH2:45]>>[C:8]([O:12][C:13](=[O:40])[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([CH3:32])[CH3:31])[C@@H:33]([OH:34])[CH2:37][C@H:36]([C:35](=[O:39])[NH:45][CH2:44][C:43]([CH3:47])([CH3:46])[CH3:42])[CH3:38])([CH3:11])([CH3:9])[CH3:10]

Participants

5

Reactant 4

HCID 962WaterHCID 79882NeopentylamineHCID 66645428{(S)-2-[2,2-Dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterHCID 178516071HCID 178516071, compound

Product 1

HCID 66645452{(1S,2S,4R)-4-(2,2-Dimethylpropylcarbamoyl)-1-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxypentyl}carbamic acid t-butyl esterYield 85%

Conditions

Temperature
80 °C

Procedure

6.8 mg of 2-hydroxypyridine (0.072 mmol) was added to a solution of 165 mg of {(S)-2-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (85b) (0.36 mmol) in (2,2-dimethylpropyl)amine (1.5 ml), and the mixture was stirred at 80° C. for 2.5 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:methylene chloride/methanol=20/1) to obtain 167 mg of the title compound (yield: 85%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
  4. filtrationAfter filtration
  5. customthe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=20/1)

Sources & evidence

ORD record
ord-ef15732eb18d4c8fa211ca77b1d52ccc
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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