3,3,3-Triphenylpropionic Acid → N-{(1S)-2-(3-{((3R)-1-cyclohexylmethyl-3-piperidyl)methyl}amino-3-oxopropyl)amino-1-(2-carbamoylethyl)-2-oxoethyl}-3,3,3-triphenylpropanamide

HRID 272069Notes

Reaction equation

HRID 272069 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:26][CH2:27][C:28]([NH:30]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:29])[C:4]([NH:6][CH2:7][CH2:8][C:9]([NH:11][CH2:12][C@H:13]1[CH2:18][CH2:17][CH2:16][N:15]([CH2:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:14]1)=[O:10])=[O:5].[C:50]1([C:56]([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[CH2:57][C:58](O)=[O:59])[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.C(N(CC)C(C)C)(C)C>[CH:20]1([CH2:19][N:15]2[CH2:16][CH2:17][CH2:18][C@H:13]([CH2:12][NH:11][C:9](=[O:10])[CH2:8][CH2:7][NH:6][C:4](=[O:5])[C@@H:3]([NH:2][C:58](=[O:59])[CH2:57][C:56]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)([C:61]3[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=3)[C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=3)[CH2:26][CH2:27][C:28](=[O:29])[NH2:30])[CH2:14]2)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1

Participants

8

Reactant 5

HCID 1366963,3,3-Triphenylpropionic AcidHCID 516892Sodium Bicarbonate2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 69101269(2S)-2-amino-N5-triphenylmethyl-N1-(3-{((3R)-1-cyclohexylmethyl-3-piperidyl)methyl}amino-3-oxopropyl)pentanediamide monohydrochloride

Product 1

HCID 12149945N-{(1S)-2-(3-{((3R)-1-cyclohexylmethyl-3-piperidyl)methyl}amino-3-oxopropyl)amino-1-(2-carbamoylethyl)-2-oxoethyl}-3,3,3-triphenylpropanamideYield 50.8%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a solution of 84 mg of (2S)-2-amino-N5-triphenylmethyl-N1-(3-{((3R)-1-cyclohexylmethyl-3-piperidyl)methyl}amino-3-oxopropyl)pentanediamide monohydrochloride in 1.5 ml of chloroform, 0.052 ml of N,N-diisopropylethylamine was added at room temperature, followed by an hour's stirring at the same temperature. Then 39 mg of 3,3,3-triphenylpropionic acid, 24 mg of 1-hydroxy-benzotriazole monohydrate and 31 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide monohydrochloride were added at room temperature by the order stated, followed by 17 hours' stirring at the same temperature. The reaction liquid was rendered weakly basic with saturated aqueous sodium bicarbonate solution, extracted with chloroform and dried over anhydrous sodium sulfate. Distilling the solvent off, the resultant residue was dissolved in 1 ml of chloroform, and to the solution 1 ml of trifluoroacetic acid was added at room temperature, followed by 20 minutes' stirring at the same temperature. The reaction liquid was rendered weakly basic with saturated aqueous sodium bicarbonate solution, extracted with chloroform and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resultant residue was purified with preparative thin layer chromatography (Kieselgel™60F254, Art 5744 (Merck), chloroform/methanol/28% aqueous ammonia=90/10/1) to provide 43 mg of the title compound as a white solid.

Workup

  1. waitfollowed by an hour
  2. stirring' stirring at the same temperature
  3. customThe reaction liquid
  4. extractionextracted with chloroform
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationDistilling the solvent off, the resultant residue
  7. dissolutionwas dissolved in 1 ml of chloroform
  8. additionto the solution 1 ml of trifluoroacetic acid was added at room temperature
  9. waitfollowed by 20 minutes
  10. stirring' stirring at the same temperature
  11. customThe reaction liquid
  12. extractionextracted with chloroform
  13. dry with materialdried over anhydrous sodium sulfate
  14. distillationThe solvent was distilled off under reduced pressure
  15. customthe resultant residue was purified with preparative thin layer chromatography (Kieselgel™60F254, Art 5744 (Merck), chloroform/methanol/28% aqueous ammonia=90/10/1)

Sources & evidence

ORD record
ord-57c4905a59c6485e908710019aec26a2
Source dataset
uspto-grants-2008_11
Patent number
US07452908B2

Reaction notes

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