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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.
H-Asp(OtBu)-OtBu·HCl is an aspartic acid derivative, potentially used for research on neurofunctional comparisons and non-alcoholic hepatitis-related metabolic diseases.
Synonyms: H-Asp(OtBu)-OtBu.HCl
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Batch number can be found on the product's label following the word 'Batch'.
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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 1791-13-5 |
Formula : | C12H24ClNO4 |
M.W : | 281.78 |
SMILES Code : | O=C(OC(C)(C)C)[C@@H](N)CC(OC(C)(C)C)=O.[H]Cl |
Synonyms : |
H-Asp(OtBu)-OtBu.HCl
|
MDL No. : | MFCD00034851 |
InChI Key : | GVLZIMQSYQDAHB-QRPNPIFTSA-N |
Pubchem ID : | 13768146 |
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 |
---|---|---|
Stir a mixture of [[[6-(3-methyl-2-pyridinyl)-1,7-naphthyridin-8-yl]amino]sulfonyl]acetic acid (457 mg, 1.27 mmol), L-aspartic acid, di-t-butyl ester hydrochloride (358 mg, 1.27 mmol) and triethylamine (0.18 mL, 1.29 mmol) in dry dichloromethane (25 mL) for 10 minutes at room temperature. Add 1-(N,N-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (293 mg, 1.53 mmol) and stir 72 h at room temperature. Remove solvent under reduced pressure, and flash chromatograph the residue, eluting with dichloromethane-methanol-concentrated ammonium hydroxide (95:5:0.1) to obtain the crude di-t-butyl ester of the title dicarboxylic acid. Dissolve the di-t-butyl ester (599 mg, 1.02 mmol) in trifluoracetic acid (2 mL) and allow the solution to stand at room temperature for 18 h. Remove solvent under reduced pressure, and partition the residue between water (5 mL) and dichloromethane (5 mL). Wash the aqueous layer successively with dichloromethane (5 mL) and diethyl ether (3 mL). Strip water from the aqueous layer under reduced pressure to obtain the crude title acid (free form). Crystallize from methanol-isopropyl ether, then reflux in methanol (25 mL), cool to room temperature and filter to obtain the analytically pure free form of the title acid, C20H19N5O7S, mp 207-208 C (dec). FABMS: MH+ 474 (12%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); at 20℃; | To H-ASP (OtBu)-OtBu hydrochloride salt (28 mg, 0.10 MMOL) in dry DMF (2 mL) was sequentially added at room temperature 2- (3-TRITYLSULFANYL-PROPYL)-SUCCINIC acid 4-TERT-BUTYL ester (50 mg, 0.10 MMOL), HOBt (14mg, 0.10 MMOL), PYBOP (56 mg, 0.11 MMOL) and DIPEA (37 uL, 0.20 MMOL). The usual aqueous work up yielded the title compound (62 mg, 86%) as a colorless residue : H NMR (CDCI3, 400 MHz) D 7.41-7. 38 (m, 6H), 7.29-7. 25 (m, 6H), 6.60-6. 57 (m, 1H), 4.68-4. 56 (m, 1H), 3.18- 3.14 (m, 2H), 2.89-2. 80 (m, 1H), 2.74-2. 52 (m, 2H), 2.43-2. 36 (m, 1H), 2.32-2. 19 (m, 1H), 2.12-2. 07 (m, 2H), 1.83-1. 80 (m, 2H), 1.60-1. 53 (m, 1H), 1.45-1. 40 (m, 27H); 13C (DEPT) (CDCI3, 100 MHz) J 129.4, 127.7, 126.4, 49.0, 48.7, 46.1, 42.5, 37.8, 37.6, 37.2, 31.6, 31.5, 29.6, 27.9, 27.8, 27.7, 26.3, 26.2, 26.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In 1,4-dioxane; water; ethyl acetate; at 5 - 10℃; for 0.5h; | [ The oil of EXAMPLE 1 above was dissolved in 130 ml of ethyl acetate (EtOAc) and added to a Fisher Porter Bottle (Andrew Glass Co., Vineland, N.J.) containing 22 ml of 5% palladium on activated carbon (Pd/C), 61.81% water (1.99 g, 2.5 wt. %) and ethyl acetate. The resulting solution, which contained Z-Asp(OtBu)2 was kept at room tempera ture, under a hydrogen pressure measured at 60 psi, for three hours. During this time, a hydrogenolysis reaction took place. Afterward, the solution was filtered over Celite (Aldrich, Milwaukee, Wis.) to separate the metal-containing catalyst. The catalyst was rinsed twice with about 30 ml of ethyl acetate for reuse. The filtrate containing L-Asp di-tert butyl amino ester (L-Asp(OtBu)2) was cooled to a temperature of about 5 C to 100 C. Then 18.9 ml (75.6 mmol) of 4M HCl (in dioxane) was added to the filtrate while stirring. The temperature of the filtrate-HCl reaction solution was maintained at a temperature of about 5 C to 10 C. After stirring for about 30 minutes, the mixture was filtered. The wet cake was washed twice, each time with 25 ml of ethyl acetate. The washed wet cake was dried by suction for 30 minutes and then dried in vacuo at a temperature of about 50 C. A white solid obtained was L-Asp di-tert-butyl amino ester hydrochloride salt (L-Asp(OtBu)2.HCl)(15.79 grams), 50% yield from Z-Asp. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 15; N-[(2R)-2-([4-((2R, 3R)-1-(4-fluorophenyl)-3-[2-(4-fluorophenyl)-2-hydroxyethyl] thio}- 4-oxoazetidin-2-yl) phenoxy] acetyl} amino)-2-phenylacetyl]-L-aspartic acid; (2R)-( { [4-((2R, 3R)-1-(4-Fluorophenyl)-3- { [2-(4-fluorophenyl)-2-oxoethyl] thio}-4- oxoazetidin-2-yl) phenoxy] acetyl} amino) (phenyl) acetic acid (0.020 g, 0.032 mmol), di-tert- butyl L-aspartate hydrochloride (0. 011 g, 0.039 mmol) and N-methyl-morpholine (0. 010 g, 0.097 mmol) were dissolved in CH2Cl2 (3 ml). After 5 minutes, TBTU (0.014 g, 0.042 mmol) was added. Full conversion to the corresponding tert-butyl ester was obtained after 1 h. The reaction mixture was purified on silica gel and eluted with EtOAc/CH2C12 (25/75). The pure fractions were collected and concentrated. The residue was dissolved in 3 ml of CH2Cl2 and 1 ml of TFA. The reaction mixture was stirred for 2h and the resulting acid was concentrated. The remaining trace of TFA was azeotropically removed by co-evaporation with toluene (3 ml). The crude acid was dissolved in MeOH (3 ml) and NaBH4 (0.005 g, 0.130 mmol) was added. Full conversion to the corresponding alcohol was obtained after 5 minutes. The reaction was quenched by the addition of 0. 1M NH40Ac buffer (2 ml). Purification by preparative HPLC using a gradient of 10-40% CH3CN in 0. 1M NH40Ac buffer as eluent followed by freeze-drying of the pure fractions afforded the title compound (0. 018 g, 76%) as a colourless solid. M/z : 715.7 (M-18). lH NMR [(CD3) 2SO), 400 MHz] 8 2.00-2. 08 (m, 1H), 2.31-2. 50 (m, 1H), 2.88-2. 94 (m, 2H), 4.18-4. 22 (m, 1H), 4. 27-4. 30 (m, 1H), 4.60-4. 78 (m,. 3H), 5.03-5. 08 (m, 1H), 5.55-5. 65 (m, 1H), 6.94-7. 40 (m, 17H), 8. 22-8.39 (m, 1H), 8. 50-8.59 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; at 0℃; for 16h; | A solution of the product of example 1D (0.44 g, 1.86 mmol), EDCI (0.391 g, 2.05 mmol), L-aspartic acid -(alpha,beta di-tert-butyl) ester hydrochloride (0.567 g, 2.05 mmol), and N-hydroxybenzotriazole (0.277 g, 2.05 mmol) in THF (20 mL) was cooled to 0 C, stirred for 16 hours, diluted with water (100 mL), and extracted with ethyl acetate. The ethyl acetate was washed with 0.5M HCl, aqueous sodium bicarbonate, and brine, dried (MgSO4), and concentrated to provide a yellow oil which was chromatographed on silica with MeOH/ Chloroform to provide the title compound (0.33 g, 38%). MS (APCI+) m/e 407 (M-t-Bu)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 72h; | Step CDi-tert-butyl (2S)-2-[(3-[5-oxido-4-(phenylsulphonyl)-1,2,5-oxadiazol-3-yl]-oxy}-propionyl)-amino]-succinate; A solution of the compound obtained in the above Step (2.7 g-8 mmol), di-tert-butyl L-aspartate hydrochloride (2.25 g-8 mmol), EDCI (1.62 g-8 mmol), DIEA (1.32 g-8 mmol) and HOBT (1.1 g-8 mmol) in 100 ml of anhydrous DMF is stirred for 72 hours at ambient temperature under argon. The DMF is removed by distillation and then the residue is taken up in 100 ml of water and 100 ml of ethyl acetate. The organic phase is then washed with 5% NaHCO3 solution, dried over Na2SO4 and then evaporated to dryness. The crude reaction product is purified by flash chromatography using as eluant a (90:10) dichloromethane/ethyl acetate mixture. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | (a) A solution of 3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenylacetic acid (50 mg), 3-ethyl-1-[3-(dimethylamino)propyl]carbodiimide hydrochloride (EDCI), (30 mg), 1-hydroxybenzotriazole hydrate (HBT), (28 mg) in dimethyl formamide (1 ml) was stirred at room temperature for 0.5 h followed by addition of a solution of L-di-t-butyl aspartate hydrochloride (52 mg) and triethylamine (32 mg) in dimethyl formamide (1 ml). After stirring for three days, the mixture was partitioned between water and ethyl acetate. The organic phase was washed with brine and then dried, filtered and concentrated. The residue was chromatographed on silica gel eluted with ethyl acetate/light petroleum ether (1:4). Pure fractions were pooled and concentrated to give L-di-t-butyl N-[3,5-dichloro-4 (4-hydroxy-3-isopropylphenoxy)phenylacetyl]aspartate (68 mg, 83%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;Cooling with ice; Inert atmosphere; | 1-Hydroxybenzotriazole (HOBT) (0.676 g, 5 mmol, 1.0 eq.) and O-benzotriazole-N,N,N',N'-tetramethyl-uronium-hexafluorophosphate (HBTU) (1.896 g, 5 mmol, 1.0 eq.) were added to 1.409 g (5 mmol) of <strong>[1791-13-5]L-<strong>[1791-13-5]aspartic acid di-tert-butyl ester hydrochloride</strong></strong> and 1.292 g (10 mmol, 2.0 eq.) of di-isopropylethylamine in 25 mL dichloromethane. Methacrylic acid (0.43 g, 5 mmol, 1.0 eq.) in 10 mL dichloromethane was added to the ice-cold solution drop wise and the reaction solution was stirred for 18 hours under nitrogen gas at room temperature. Solution was washed with 10% brine and the organic layer was collected. Aqueous 10% citric acid (2X) was used for washing next and the organic layer collected was treated with 4% sodium bicarbonate solution (2X). The organic layer was dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The solid mass was purified using automated flash chromatography over silica gel with ethylacetate/hexane (Rf = 0.5; EtOAc : Hex = 1:1) as the mobile phase. White crystalline solids were obtained as the purified product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of 4-vinylbenzoic acid (1.036 g, 7 mmol), <strong>[1791-13-5]L-<strong>[1791-13-5]aspartic acid di-tert-butyl ester hydrochloride</strong></strong> (1.453 g, 7 mmol), 1-hydroxybenzotriazole (HOBT) (0.947 g, 7 mmol) and O-benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) (2.676 g, 7 mmol) in dichloromethane was stirred under nitrogen gas at room temperature for 15 minutes. N,N-diisopropylethylamine (2.37 g, 14 mmol) was then added to the solution and stirred overnight under nitrogen gas at room temperature. Solution was washed with 15% brine, 20% citric acid solution, and 7% sodium carbonate solution. The solvent was then removed under reduced pressure. The product was purified using automated flash chromatography over silica gel using dichloromethane/methanol (Rf = 0.9; 90% dichloromethane/10% methanol) as the mobile phase. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.2% | With diethyl cyanophosphonate; triethylamine; trifluoroacetic acid; In dichloromethane; at 20℃; for 12h; | 0.4 g (1.0 mmol) compound 2 is dissolved in 10.0 mL dry trifluoacetic acid. 0.7 mL triethylamine (5.0 mmol), 0.3g hydrochloric acid ditertiarybutyl-L-aspartic ester (1.0 mmol) and 0.2 mL phosphoryl cyanide are added sequentially at room temperature into the dichloromethane solution. The solution is stirred for 12 hours. 20 mL dichloromethane is then added into the mixture. The reaction mixture is washed with water twice (20-30 mL each time) and dried with MgSO4. The final products are separated using silica gel column. Dichloromethane and ethanol are in the mobile phase in a volume ratio of 95:5. 0.48g compound 4 is obtained (product yield: 79.2%). |