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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 21947-98-8 |
Formula : | C27H29NO4S |
M.W : | 463.59 |
SMILES Code : | O=C(O)[C@H](CSC(C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)NC(OC(C)(C)C)=O |
MDL No. : | MFCD00038251 |
InChI Key : | JDTOWOURWBDELG-QHCPKHFHSA-N |
Pubchem ID : | 11167161 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | To a solution of 2[36] and [37] (5 g, 12.7 mmol) in NaOH 2N (80 mL) was added Boc2O (4.5 g, 20 mmol) and the reaction mixture was stirred at room temperature for 24 h. The aqueous solution was then acidified with HCl concentrated until pH 2 and extracted with CH2Cl2 (2 .x. 100 mL); the combined organic phases were washed with brine, dried and concentrated under reduce pressure to give without any further purification compound 3 (5.3 g, 90percent) as white foam.1H NMR (DMSO): delta (ppm) 1.37 (s, 9H, 3 .x. CH3); 2.29-2.58 (m, 2H, CH2); 3.76-3.79 (m, 1H, CH); 6.84 (d, J = 7.8 Hz, 1H, NH); 7.14-7.38 (m, 15H, trityl-H).MALDI-TOF MS: m/z 464.8 Da [M + H], C27H29NO4S, Mol. Wt.: 463.59. | |
86.21% | With sodium hydroxide; In 1,4-dioxane; water; at 20℃; for 8h;Cooling with ice; | The compound <strong>[2799-07-7]S-trityl-L-cysteine</strong> (5 g, 13.76 mmol)Was dissolved in dioxane (40 ml)Water (20 ml),1M sodium hydroxide solution (14 ml)Stir under ice bath,Boc-anhydride (3.5 ml, 15.14 mmol) was added,The reaction naturally rose to room temperature,Stirring for 8 hours,TLC detection reaction is completed,The reaction mixture was concentrated to 20-25 ml,Ethyl acetate was added,A solution of sodium bisulfate was added dropwise under stirring in an ice bath,After adjusting the pH to 2-3,Extracted with ethyl acetate,The organic layer was washed with saturated brine,Then dried over sodium sulfate,concentrate,Column chromatography (methanol: dichloromethane 1percent -5percent),The product was a white solid (5.5 g, yield: 86.21percent). |
60% | To the solution of Trt-Cys-OH (22.68 g, 62.5 mmol) in dioxane (60 mL) and water (125 mL) was added di-tert-butyldicarbonate (41 g, 187 mmol) at 45 0C, and the solution was adjusted with NaOH(4M) until pH = 9.5, and then stirred at the same temperature overnight. Once the reaction was done, water and dioxane was removed under reduced pressure. The residue was dissolved into water (150 mL) , extracted with ethyl acetate (2 x 100 mL) . The aqueous layer was adjusted to pH = 2 with dilute HCl while in an ice bath, and then the aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried over magnesium sulfate. Removal of the solvent under vacuum yielded a yellow oil. The residue was then dissolved into ethyl ether and carefully added a 1 : 1 mixture of ethyl ether and hexane while stirring to <n="32"/>precipitate out the white solid in 60percent yield. Ic: 1H NMR (300 MHz, CDC13): deltal.46 (s, 9H), 2.69 (br, 2H), 4.21 (s, IH), 4.97 (s, IH), 7.20-7.44 (m, 15H), 10.2 (br, IH); 13C NMR (75.5 MHz, CDC13): delta 28.1, 33.5, 52.4, 144.1, 155.4, 175.1 |
With sodium hydroxide; at 20℃; for 24h; | (1) 1.1 g of <strong>[2799-07-7]S-trityl-L-cysteine</strong> (II), 1.0 g of di-tert-butyl dicarbonate (Boc2O) and 19 mL of 2N aqueous sodium hydroxide were mixed and allowed to react at room temperature for 24 hours. Drop to room temperature, slowly dropping 1mol / L HCl to adjust pH = 2,The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with distilled water to a pH of 7. The organic layer was dried over anhydrous sodium sulfate and removed with water. The filtrate was collected by filtration and the filtrate was evaporated to remove the extractant to give a white foamy solid amino-S-Trityl-Cys (III). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dicyclohexyl-carbodiimide; In acetonitrile; at 0 - 20℃; for 17.5h;Inert atmosphere; | Boc-L-Cys(Trt)-OH (0.1 g, 0.22 mmol, 1.0 eq.) and <strong>[50595-15-8]tert-butyl-2-hydroxyacetate</strong> (55.6 mg, 0.42 mmol, 1.95 eq.) were stirred in anhydrous acetonitrile at 0 °C, to this N,N?dicyclohexylcarbodiimide (86.8 mg, 0.42 mmol, 1.95 eq.) was added and the resulting solution stirred under argon at 0 °C for a further 2 h before being stirred at RT for 15.5 h. After this time, the reaction mixture was filtered under reduced pressure, the filtrate was concentrated in vacuo and the resulting residue was adsorbed onto Celite® and purified by silica gel chromatography, eluting with ethyl acetate and petroleum ether (5:95 - 40:60; ethyl acetate : petroleum ether) to yield 2-(tert-butoxy)-2-oxoethyl N-(tert-butoxycarbonyl)S-trityl-L-cysteinate as an impure oil (0.11 g), which was used without further purification. N(tert-butoxycarbonyl)-S-trityl-L-cysteinate (0.11 g) and triethylsilane (0.08 g, 0.11 mL, 0.69 mmol) were stirred under argon at RT in 20percent TFA in CH2C12 (6.5 mL) for 2 h. After this time the reaction solution was concentrated in vacuo and the resulting residue was purified by RP c-i 8 silica gel column chromatography, eluting with water to afford 2-((L-cysteinyl)oxy)acetic acid as an impure colourless solid (32.2 mg), which was used without further purification. To 2-((L-Cysteinyl)oxy)acetic acid (32.2 mg) stirring in water (3.6 mL) was added N-tert-butyl-maleimide (27.5 mg, 26.0 1iL, 0.18 mmol) and the resulting solution was stirred at RT for 7 h. After this time, the reaction solution was lyophilized and the resulting solid was purified by semi-preparative HPLC (Agilent ZORBAX 300SB-C18 column; 95:5:0.1 - 5:95:0.1; H20 : MecN : TFA) to afford (2R)-3-((i-(tert-butyl)-2,5- dioxopyrrolidin-3 -yl)thio)- 1 -(carboxymethoxy)- 1 -oxopropan-2-aminium 2,2,2- trifluoroacetate (mixture of diastereoisomers) as a colourless solid (25.5 mg), which was used without further purification. |
Tags: Boc-Cys(Trt)-OH | (R)-2-((tert-Butoxycarbonyl)amino)-3-(tritylthio)propanoic acid | Aryls | Sulfides | Carboxylic Acids | Carbamates | Esters | Organic Building Blocks | 21947-98-8
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