* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
EXAMPLE 39 N-Z-N'-{N-(2S,3S)-trans-ethoxycarbonyloxirane-2-carbonyl]-o-fluoro-L-phenylalanyl}-1,4-diaminobutane In a mixture of dioxanes (10 ml) and water (5 ml), o-fluoro-L-phenylalanine (1.00 g, manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved. To the solution were added, while stirring under ice-cooling conditions, a 1N aqueous solution of sodium hydroxide (5.46 ml) and di-tert-butyl dicarbonate (1.38 ml), followed by stirring for one hour at room temperature. The reaction mixture was concentrated, then the pH was adjusted to 2.5, followed by extraction with ethyl acetate (100 ml *3). The ethyl acetate layer was washed with water and a saturated saline, dried over anhydrous sodium sulfate. After concentration, the concentrate was crystallized from ethyl acetate--petroleum ether to yield N-Boc-o-fluoro-L-phenylalanine (1.32 g) as colorless crystals (yield 85percent).
Reference：
[1] Patent: US5556853, 1996, A,
[2] Journal of Medicinal Chemistry, 1994, vol. 37, # 13, p. 2090 - 2099
2
[ 58632-95-4 ]
[ 19883-78-4 ]
[ 114873-00-6 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1989, vol. 37, # 3, p. 826 - 828
EXAMPLE 39 N-Z-N'-{N-(2S,3S)-trans-ethoxycarbonyloxirane-2-carbonyl]-o-fluoro-L-phenylalanyl}-1,4-diaminobutane In a mixture of dioxanes (10 ml) and water (5 ml), o-fluoro-L-phenylalanine (1.00 g, manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved. To the solution were added, while stirring under ice-cooling conditions, a 1N aqueous solution of sodium hydroxide (5.46 ml) and di-tert-butyl dicarbonate (1.38 ml), followed by stirring for one hour at room temperature. The reaction mixture was concentrated, then the pH was adjusted to 2.5, followed by extraction with ethyl acetate (100 ml *3). The ethyl acetate layer was washed with water and a saturated saline, dried over anhydrous sodium sulfate. After concentration, the concentrate was crystallized from ethyl acetate--petroleum ether to yield N-Boc-o-fluoro-L-phenylalanine (1.32 g) as colorless crystals (yield 85%).
(R)-N-{(S)-2-(2-Fluoro-phenyl)-1-[(S)-4-guanidino-1-(thiazole-2-carbonyl)-butylcarbamoyl]-ethyl}-3-phenyl-2-phenylmethanesulfonylamino-propionamide[ No CAS ]
(R)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-5-guanidino-pentanoic acid ([(S)-1-carbamoyl-2-(2-fluoro-phenyl)-ethyl]-ethyl-carbamoyl}-methyl)-amide; compound with acetic acid[ No CAS ]
(S)-2-tert-Butoxycarbonylamino-3-(2-fluorophenyl)-1-thiazolidin-3-yl-propan-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
A. (S)-2-tert-Butoxycarbonylamino-3-(2-fluorophenyl)-1-thiazolidin-3-yl-propan-1-one From L-Boc-2-fluorophenylalanine and 4-hydroxypiperidine by a method analogous to Procedure C.
5-(1S-1-(3,5-dicarboxyphenylaminocarbonyl)-2-(2-fluorophenyl)ethylaminocarbonyl)-6-(cycloheptanemethylaminocarbonyl)benzimidazole disodium salt[ No CAS ]
General procedure: (S)-2-((tert-Butoxycarbonyl)amino)-3-phenylpropanoic acid (compound 5a, 203.6 mg, 0.768 mmol) in DMF (5 mL) was added HOBt (283.2 mg, 2.10 mmol) and EDCI (257.8 mg, 1.396 mmol). After stirring for 30 min compound 4 (187.2 mg, 0.698 mmol) and additional TEA (0.30 mL, 2.10 mmol) were added. This solution was allowed to stir at room temperature for 20 h and then the saturated NaHCO3 was added. The mixture was extracted with EtOAc and washed with saturated NaCl, dried over Na2SO4 and concentrated. The residue was purified with flash chromatography on silica gel, eluted with a mixture of PE/EA (4/1, v/v) to afford 6a (130 mg, 54%) as a white solid.
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0 - 20℃; for 12h;
To Boc-Aib-Leu-OMe (1), (1.75 g, 5.31mmol), trifluoroacetic acid (3 mL) was added at 0 C and stirred at room temperature. The removal of the Boc-group was monitored by TLC. After 12 hrs the trifluoroacetic acid was removed under reduced pressure to afford the crude trifluoroacetate salt. The residue was taken up in water and washed with diethyl ether. The pH of the aqueous solution was adjusted to 8 with sodium bicarbonate and extracted with ethyl acetate. The extracts were pooled, washed with saturated brine, dried over sodium sulphate, and concentrated to a highly viscous liquid that gave a positive ninhydrin test. This tripeptide free base was added to a well ice-cooled solution of Boc-(2F)-Phe-OH(1.0 g, 3.54 mmol) in DMF (4 mL) followed by HATU(1.35, 3.54 mmol) and DIPEA (2 mL). The reaction mixture was stirred at room temperature for 12 h. The residue was taken up in ethyl acetate. The organic layer was washed with 2M HCl (3 x 50 mL), 1M Na2CO3 solution (3 x 50 mL) and brine, dried over anhydrous Na2SO4 and evaporated in vacuo, to yield a white solid. Purification was done using silica gel as stationary phase and ethyl acetate-petroleum ether mixture as the eluent. Single crystals were grown from acetone to petroleum ether mixture by slow evaporation and were stable at room temperature.
(S)-2-amino-3-(2-fluorophenyl)-N-((R)-3-methyl-1-((3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)butyl)propanamide hydrochloride[ No CAS ]
2,5-dichloro-N-((S)-3-(2-fluorophenyl)-1-(((R)-3-methyl-1-((3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)butyl)amino)-1-oxopropan-2-yl)benzamide[ No CAS ]
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
