| Identification | Back Directory | [Name]
Boc-HPh-Leu-Phe-OMe | [CAS]
868539-96-2 | [Synonyms]
Boc-HPh-Leu-Phe-OMe
Carfilzomib Impurity 70
methyl ((S)-2-((tert-butoxycarbonyl)amino)-4-phenylbutanoyl)-L-leucyl-L-phenylalaninate
N-[(S)-2-(tert-Butoxycarbonylamino)-4-phenylbutanoyl]-L-leucyl-L-phenylalanine methyl ester
L-Phenylalanine, (αS)-α-[[(1,1-dimethylethoxy)carbonyl]amino]benzenebutanoyl-L-leucyl-, methyl ester
(S)-methyl 2-((S)-2-tert.butoxycarbonyIamino-4-phenylbutanamido-4-methylpentanamido)-3-phenylpropanoate
Methyl N-[(2S)-2-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)-4-phenylbutanoyl]-L-leucyl-L-phenylalaninate
(6S,9S,12S)-Methyl 12-benzyl-9-isobutyl-2,2-dimethyl-4,7,10-trioxo-6-phenethyl-3-oxa-5,8,11-triazatridecan-13-oate | [Molecular Formula]
C31H43N3O6 | [MDL Number]
MFCD28167958 | [MOL File]
868539-96-2.mol | [Molecular Weight]
553.7 |
| Chemical Properties | Back Directory | [Boiling point ]
753.4±60.0 °C(Predicted) | [density ]
1.123±0.06 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,2-8°C | [pka]
11.22±0.46(Predicted) | [Appearance]
White Solid |
| Hazard Information | Back Directory | [Synthesis]
1. Dissolve NBoc leucine (11.56 g, 50.0 mmol) and phenylalanine methyl ester (10.78 g, 50.0 mmol) in 500 mL of DMF, add hydroxybenzotriazole (HOBT) (10.81 g, 80.0 mmol) and N,N-diisopropylethylamine (DIEA) (25.85 g, 35 mL, 200.0 mmol).
2. The reaction mixture was cooled to 0 °C in an ice-water bath and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) (35.38 g, 80.0 mmol) was added in batches over 5 min.
3. The reaction mixture was stirred overnight under argon protection.
4. Upon completion of the reaction, the reaction mixture was diluted with 1000 mL of brine and extracted with ethyl acetate (EtOAc) (5 x 200 mL).
5. The organic layers were combined, washed sequentially with water (10 x 100 mL) and brine (2 x 150 mL) and dried with anhydrous magnesium sulfate (MgSO4).
6. Remove MgSO4 by filtration and concentrate under reduced pressure to remove solvent to obtain Compound A (18.17 g).
7. Compound A (18.0 g, 45.86 mmol) was dissolved in 50 mL of 80% trifluoroacetic acid (TFA)/dichloromethane (DCM) solution pre-cooled to 0 °C. The reaction mixture was stirred and dried with anhydrous magnesium sulfate (MgSO4).
8. The reaction mixture was stirred and slowly warmed to room temperature over 2 hours.
9. Concentrate under pressure to remove volatiles and obtain an oil.
10. Boc-D-homophenylalanine (BocNHhPhe) (12.81 g, 45.86 mmol), DMF (500 mL), HOBT (9.91 g, 73.37 mmol), and DIEA (23.70 g, 32.0 mL, 183.44 mmol) were added to the oily mass.
11. The reaction mixture was cooled to 0 °C in an ice-water bath and BOP (32.45 g, 73.37 mmol) was added in batches over 5 min.
12. The reaction mixture was stirred overnight under argon protection and slowly warmed to room temperature.
13. Upon completion of the reaction, the reaction mixture was diluted with 1500 mL of water and extracted with dichloromethane (DCM) (5 x 300 mL).
14. The organic layers were combined, washed sequentially with water (6 x 300 mL) and brine (1 x 300 mL) and dried with anhydrous magnesium sulfate (MgSO4).
15. Remove MgSO4 by filtration and concentrate under reduced pressure to remove the solvent to obtain a yellow solid.
16. The yellow solid was dissolved in 200 mL of 95% ethanol (EtOH) and heated to 65 °C to dissolve the solid completely.
17. The hot solution was slowly poured into 1000 mL of cold water and the precipitate was collected to give compound B (21.59 g). | [References]
[1] Patent: KR2015/131405, 2015, A. Location in patent: Paragraph 0447-0450
[2] Journal of Medicinal Chemistry, 2018, |
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