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3-(6-Bromopyridin-2-yl)-2-cyano-3-((2,3-dihydroxypropyl)thio)-N-((S)-1-phenylbutyl)propanamide (20). Thioglycerol (42 muL, 0.5 mmol) was added to a stirred solution of <strong>[856243-80-6]WP1130</strong> (19 mg, 0.05 mmol) in acetonitrile (0.5 mL). The resulting mixture was stirred at room temperature for 17 hours. The mixture was distributed between water and dichloromethane. The separated organic layer was washed with sat. brine, dried over sodium sulfate, and concentrated to an oil. Purification by preparative TLC eluting with hexanes/ethyl acetate (6:4) afforded 20 (20 mg, 82%) as a clear oil: MS (ES+) m/z 492.0 (M+H)+.
3-(6-bromopyridin-2-yl)-2-cyano-3-(2,3-dihydroxy-4-mercaptobutylsulfanyl)-N-(1-phenylbutyl)propionamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In acetonitrile; at 20℃; for 20.0h;
3-(6-Bromo-pyridin-2-yl)-2-cyano-3-(2,3-dihydroxy-4-mercapto-butylsulfanyl)-N-(1-phenyl-butyl)-propionamide (19): A solution of <strong>[856243-80-6]WP1130</strong> (18; 0.05 g, 0.13 mmol) in acetonitrile (6 mL) was added to a stirred solution of dithiothreitol (2 g, 13 mmol) in acetonitrile (13 mL) at room temp. After 20 hours TLC [Hxa/EtOAc 1:1] showed a single product and no starting material. The mixture was filtered through a short column of silica gel in acetonitrile, and the filtrate stripped of solvent under reduced pressure. A colorless syrup was obtained. The syrup was dissolved in ethyl acetate and flash chromatographed on a column (35×70 mm) of silica gel in ethyl acetate to afford a clear yellow oil (0.02 g) which began to crystallize upon standing. Mass spec ES+; m/z=560, 562 (m+23) and 538, 540 (m+1).
(E)-3-(6-bromopyridin-2-yl)-2-cyano-N-(S)-(1-phenylbutyl)acrylamide-Human Serum Albumin adduct[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In water; acetonitrile; at 37℃; for 48.0h;
Human serum albumin (HSA) (665 mg, 0.1 mmol) loaded into a 40 mL scintillation vial and then distilled water was added (3.0 mL). The mixture was heated at 37C until all of the HSA was dissolved (clear, yellow/beige solution). To the mixture was added WPl 130 (7.68 mg, 0.2 mmol) in acetonitrile (0.2 mL). The mixture was sonicated for 10 mins and heated at 37C in a rotary shaker bath. The heating was continued until WPl 130 was no longer observed by LCMS (48 hrs). The water and volatiles were evaporated and the resulting powder was dried under vacuum for 24 hrs. The resulting powder was pressed using a mortar and pestle to give a pale yellow powder.
With 3-amino propanoic acid; In ethanol; water; at 20℃;
To a mixture of cyanoacetic acid (1.0 g, 11.8 mmol) and 1- [bis(dimethylamino)methylene] - 1 H- 1 ,2,3 -triazolo [4,5 -b]pyridinium 3 -oxid hexafluorophosphate (HATU) (4.48 g, 11.8 mmol) in dichloromethane (5 mL) was added 1-phenylcyclopentan-l- amine (81 mg, 0.5 mmol), followed by N,N-diisopropylethylamine (4.1 mL, 23.6 mmol). The mixture was stirred at room temperature for overnight then evaporated to dryness. The residue was extracted with EtOAc and water. The organic layer was separated, washed with brine, dried over Na2S04 and concentrated to dryness. The residue was re-dissolved in a mixture of EtOH (2 mL) and water (2 mL). To the mixture was then added beta-alanine (8.4 g, 94.4 mmol), followed by 6-bromo-2-pyridinecarboxaldehyde (4.4 g 23.6 mmol). The resulting mixture was then stirred at room temperature overnight and a white precipitate formed. The product was then collected via filtration, and rinsed with a solution of 1 : 1 EtOH: water 3X to afford WP1130 as a white solid (3.2 g). LCMS MH+=384