Trifluoroacetic acid → (2S,4S,5S)-5-Amino-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid butylamide fumarate

HRID 1694901Notes

Reaction equation

HRID 1694901 reaction equation
FC(F)(F)C(O)=O.C(OC(=O)[NH:14][C@@H:15]([CH2:30][N:31]1[CH2:36][C:35](=[O:37])[N:34]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[Cl:44])[CH2:33][C:32]1([CH3:46])[CH3:45])[C@@H:16]([OH:29])[CH2:17][C@H:18]([C:22](=[O:28])[NH:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH:19]([CH3:21])[CH3:20])(C)(C)C.[C:48]([OH:55])(=[O:54])/[CH:49]=[CH:50]/[C:51]([OH:53])=[O:52].C(NC(=O)[C@H](C(C)C)C[C@H](O)[C@@H](N)CN1CC(=O)N(C2C=CC=CC=2Cl)CC1(C)C)CCC>C(Cl)Cl.CO>[C:48]([OH:55])(=[O:54])/[CH:49]=[CH:50]/[C:51]([OH:53])=[O:52].[CH2:24]([NH:23][C:22](=[O:28])[C@H:18]([CH:19]([CH3:21])[CH3:20])[CH2:17][C@H:16]([OH:29])[C@@H:15]([NH2:14])[CH2:30][N:31]1[CH2:36][C:35](=[O:37])[N:34]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[Cl:44])[CH2:33][C:32]1([CH3:45])[CH3:46])[CH2:25][CH2:26][CH3:27]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 444972Fumaric AcidHCID 23726071HCID 23726071, compoundHCID 66645740{(1S,2S,4S)-4-Butylcarbamoyl-1-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester

Product 1

HCID 66645588(2S,4S,5S)-5-Amino-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid butylamide fumarateYield 86.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

0.86 ml of trifluoroacetic acid (11 mmol) was added to a solution of 215 mg of {(1S,2S,4S)-4-butylcarbamoyl-1-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester obtained in Example (4a) (0.37 mmol) in methylene chloride (1.7 ml) at room temperature, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure and diluted with a saturated sodium bicarbonate aqueous solution, 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/triethylamine=200/20/1). 35.2 mg of fumaric acid (0.30 mmol) was added to a solution of 146 mg of (2S,4S,5S)-5-amino-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid butylamide obtained above (0.30 mmol) in methanol (3 ml), and the mixture was stirred at room temperature for five minutes. The solvent was evaporated under reduced pressure to obtain 155 mg of the title compound (yield: 71%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with a saturated sodium bicarbonate aqueous solution
  3. extractionfollowed by extraction with methylene chloride
  4. dry with materialThen, the organic layer was dried over anhydrous magnesium 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/triethylamine=200/20/1)
  8. stirringthe mixture was stirred at room temperature for five minutes
  9. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-9a916bca70e1407b9f96a9c8f8685f18
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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