Trifluoroacetic acid → 4-Amino-cyclohexanecarboxylic acid N-methyl-N-((1R)-1-[N-methyl-N-{(1R)-1-methylcarbamoyl-2-phenylethyl}-carbamoyl]-2-(2-naphthyl)ethyl)amide

HRID 1268604Notes

Reaction equation

HRID 1268604 reaction equation
C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:45])[N:15]([CH3:44])[C@@H:16]([C:28](=[O:43])[N:29]([C@@H:31]([C:39](=[O:42])[NH:40][CH3:41])[CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH3:30])[CH2:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)[CH2:10][CH2:9]1)(C)(C)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:44][N:15]([C@@H:16]([C:28](=[O:43])[N:29]([CH3:30])[C@@H:31]([C:39](=[O:42])[NH:40][CH3:41])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:17][C:18]1[CH:27]=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=1)[C:14]([CH:11]1[CH2:12][CH2:13][CH:8]([NH2:7])[CH2:9][CH2:10]1)=[O:45]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 54233863(4-[N-Methyl-N-{(1R)-1-(N-methyl-[(1R)-1-(methylcarbamoyl)-2-phenylethyl]carbamoyl)-2-(2-naphthyl)-ethyl}-carbamoyl]cyclohexyl)carbamic acid tert-butyl ester

Product 1

HCID 118003104-Amino-cyclohexanecarboxylic acid N-methyl-N-((1R)-1-[N-methyl-N-{(1R)-1-methylcarbamoyl-2-phenylethyl}-carbamoyl]-2-(2-naphthyl)ethyl)amideYield 49.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (4-[N-Methyl-N-{(1R)-1-(N-methyl-[(1R)-1-(methylcarbamoyl)-2-phenylethyl]carbamoyl)-2-(2-naphthyl)-ethyl}-carbamoyl]cyclohexyl)carbamic acid tert-butyl ester (240 mg, 0.38 mmol) in 1 ml dichloromethane was added 0.5 ml trifluoroacetic acid and the mixture was stirred for 5 min. Sodium bicarbonate was added until gas evolution has ceased, and the mixture was extracted with dichloromethane (3×15 ml). The combined organic phases were washed with brine (5 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was chromatographed on silica (16 g) with dichloromethane/methanol (4:1). The obtained product was dissolved in 3 ml of methanol and added 40 ml of water and 0.5 ml of acetic acid and lyophilized to give 99 mg of the title compound.

Workup

  1. extractionthe mixture was extracted with dichloromethane (3×15 ml)
  2. washThe combined organic phases were washed with brine (5 ml)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was chromatographed on silica (16 g) with dichloromethane/methanol (4:1)
  6. dissolutionThe obtained product was dissolved in 3 ml of methanol
  7. additionadded 40 ml of water and 0.5 ml of acetic acid

Sources & evidence

ORD record
ord-d96e372df46e43fe84e999c7fca2988f
Source dataset
uspto-grants-2003_04
Patent number
US06555570B2

Reaction notes

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