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Chemical Structure| 108466-89-3

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Boc-NH-PEG2-CH2COOH is a 2-unit PEG derivative with a Boc-protected amino group and a C2-carboxylic acid group. It is ideal for peptide conjugation and drug delivery systems.

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Product Citations

Rathje, Oliver H. ; Perryman, Lara ; Payne, Richard J. ; Hamprecht, Dieter W. ;

Abstract: Mixed Lineage Kinase domain-Like pseudokinase (MLKL) is implicated in a broad range of diseases due to its role as the ultimate effector of necroptosis and has therefore emerged as an attractive drug target. Here, we describe the development of PROteolysis TArgeting Chimeras (PROTACs) as a novel approach to knock down MLKL through chem. means. A series of candidate degraders were synthesized from a high-affinity pyrazole carboxamide-based MLKL ligand leading to the identification of a PROTAC mol. that effectively degraded MLKL and completely abrogated cell death in a TSZ model of necroptosis. By leveraging the innate ability of these PROTACs to degrade MLKL in a dose-dependent manner, the quant. relationship between MLKL levels and necroptosis was interrogated. This work demonstrates the feasibility of targeting MLKL using a PROTAC approach and provides a powerful tool to further our understanding of the role of MLKL within the necroptotic pathway.

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Product Details of Boc-AEEA-OH

CAS No. :108466-89-3
Formula : C11H21NO6
M.W : 263.29
SMILES Code : CC(C)(C)OC(NCCOCCOCC(O)=O)=O
MDL No. :MFCD17019374
InChI Key :OMBVJVWVXRNDSL-UHFFFAOYSA-N
Pubchem ID :2755940

Safety of Boc-AEEA-OH

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of Boc-AEEA-OH

* 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.

  • Downstream synthetic route of [ 108466-89-3 ]

[ 108466-89-3 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 6066-82-6 ]
  • [ 108466-89-3 ]
  • [ 911102-04-0 ]
YieldReaction ConditionsOperation in experiment
96% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20℃; for 16h;Inert atmosphere; To a round bottom flask were added acid 33 (640 mg, 2.43 mmol), N- hydroxysuccinimide (419 mg, 3.64 mmol), DMAP (30 mg, 0.25 mmol), and 10 mL CH2CI2 under N2. The mixture was cooled down to 0 C and then a solution of DCC (752 mg, 3.64 mmol) in 10 mL CH2CI2 was added dropwise. The mixture was allowed to warm up to room temperature slowly overnight (16 h). Lots of white precipitates formed during the reaction. The precipitates were filtered off and the filtrate was washed with 20 mL 0.05 N HCl(aq) twice. The organic layer was dried with Na2S04 and concentrated under vacuum. The residue was dispersed in 20 mL EtOAc, and the insoluble precipitates were filtered off. The filtrate was concentrated to give T2 as a colorless oil (840 mg, 96%). NMR (400 MHz, CDCL): d 4.99 (s, 1H), 4.51 (s, 2H), 3.81-3.64 (m, 4H), 3.54 (t, J= 5.2 Hz, 2H), 3.32 (br q, J= 5.2 Hz, 2H), 2.86 (s, 4H), 1.44 (m, 9H).
91% With diisopropyl-carbodiimide; In tetrahydrofuran; at 20℃; for 2h; Boc-AEEA-OH (26.4 g, 100 mmol) and HOSu (12.6 g, 110 mmol) were dissolved in 200 ml tetrahydrofuran. DIC (13.9 g, 110 mmol) was added dropwise under a condition of ice bath, and the reaction was continued at room temperature for 2 h after the dropwise addition. TLC showed that the reaction of the raw materials was completed. A vacuum concentration was performed, and the residue was recrystallized with EA to obtain 33.0 g of Boc-AEEA-OSu with yield: 91%, purity: 96.7%, MS: 361.4 (M+1).
  • 2
  • [ 305-53-3 ]
  • [ 139115-91-6 ]
  • [ 108466-89-3 ]
  • 4
  • [ 108466-89-3 ]
  • 2-[2-(2-amino-ethoxy)-ethoxy]-<i>N</i>-{2-[2-(6-chloro-hexyloxy)-ethoxy]-ethyl}-acetamide [ No CAS ]
  • 5
  • [ 108466-89-3 ]
  • [ 920264-36-4 ]
  • 7
  • [ 108466-89-3 ]
  • Acetic acid (2R,3S,4R,5R,6S)-3-acetoxy-2-acetoxymethyl-5-acetylamino-6-[4-({2-[2-(2-tert-butoxycarbonylamino-ethoxy)-ethoxy]-acetylamino}-methyl)-phenoxy]-tetrahydro-pyran-4-yl ester [ No CAS ]
  • 8
  • [ 108466-89-3 ]
  • Acetic acid (2R,3S,4R,5R,6S)-3-acetoxy-2-acetoxymethyl-5-acetylamino-6-[4-({2-[2-(2-amino-ethoxy)-ethoxy]-acetylamino}-methyl)-phenoxy]-tetrahydro-pyran-4-yl ester; hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Synthesis of 8-tert-butyloxycarbonylamino-3,6-dioxaoctanoic acid (7) This compound was prepared in 83percent overall yield (4.3 g) as a thick yellow oil from 8-chloro-3,6-dioxaoctan-1-ol (3.35 g, 20.0 mmol) using Boc-carbonate (4.36 g, 20 mmol) in place of Fmoc-Cl in the procedure described above. 1H NMR (CDCl3) delta 4.18 (s, 2H), 4.2 (s, 2H), 3.34-3.77 (m, 8H), 1.5 (s, 9H). ESI-MS 264.1 (M+H+) (Calcd. 263.1).
  • 10
  • [ 24424-99-5 ]
  • [ 134978-97-5 ]
  • [ 108466-89-3 ]
YieldReaction ConditionsOperation in experiment
62.1% With sodium carbonate; In 1,4-dioxane; water; at 20℃; for 12h; Step 3a: To a stirred solution of compound 1a (5.0 g, 30.6 mmol) in 1,4-Dioxane (50 mL), Sodium carbonate (8.12 g, 76.5 mmol, dissolved in 10 mL water) and (Boc)2O (9.98 mL, 45.7 mmol) were added and stirred at room temperature for 12 h. The progress of reaction was monitored by TLC. The reaction mass was partitioned between diethyl ether and water. Then aqueous layer was made acidic (pH=3) by 3N HCl solution and was extracted with DCM (2×200 mL). Organic layer was washed with water, brine, dried over Na2SO4 and evaporated under reduced pressure to yield 50 g of pure 3a (Yield: 62.1%). LCMS: 263.0 (M+H)+
62.1% With sodium carbonate; In 1,4-dioxane; water; at 20℃; for 12h; To a stirred solution of compound la (5.0 g, 30.6 mmol) in 1,4-Dioxane (50 mL), Sodium carbonate (8.12 g, 76.5 mmol, dissolved in 10 mL water) and (Boc)20 (9.98 mL, 45.7 mmol) were added and stirred at room temperature for 12 h. The progress ofreaction was monitored by TLC. The reaction mass was partitioned between diethyl ether and water. Then aqueous layer was made acidic (pH = 3) by 3N HC1 solution and was extracted with DCM (2 x 200 mL). Organic layer was washed with water, brine, dried over Na2504 and evaporated under reduced pressure to yield 50 g of pure 3a (Yield:62.1%). LCMS: 263.0 (M+H).
  • 11
  • (2-(2-aminoethoxy)ethoxy)acetic acid methyl ester [ No CAS ]
  • [ 108466-89-3 ]
  • [ 1100909-84-9 ]
  • 12
  • [ 707542-11-8 ]
  • [ 108466-89-3 ]
  • [ 1154625-12-3 ]
  • 13
  • boc-Gly-Merrifield resin [ No CAS ]
  • [ 15761-39-4 ]
  • [ 13734-41-3 ]
  • [ 13836-37-8 ]
  • [ 54613-99-9 ]
  • [ 81-88-9 ]
  • [ 108466-89-3 ]
  • [ 1229593-79-6 ]
  • 14
  • C117H140Cl4N27O23PolS [ No CAS ]
  • [ 108466-89-3 ]
  • C128H159Cl4N28O28PolS [ No CAS ]
  • 15
  • C36H45N3O10*H(1+) [ No CAS ]
  • [ 108466-89-3 ]
  • [ 1246261-24-4 ]
YieldReaction ConditionsOperation in experiment
90% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; To a solution of Lys-Urea-Glu (0.103 g, 0.121 mmol, Banerjee et al J Med.Chem., vol. 51, pp. 4507-4517, 2008) in DMF (2 mL) was added Boc-NH-PEG-COOH (0.060 g, 0.135 mmol) and TBTU (0.04Og, 0.125 mmol), followed by W-diisopropylethylamine (0.042 mL, 0.241 mmol). After stirring overnight at room temperature, the solvent was evaporated on a rotary evaporator. The crude material was purified by a silica column using methanol/methylene chloride (5:95) to afford 0.101 g (0.109 mmol, 90percent) of YC-VI-53, which was dissolved in a solution of 3percent anisole in TFA (1 mL). The mixture was reacted at room temperature for 10 min, then concentrated on a rotary evaporator. The crude material was purified by HPLC (Econosphere Cl 8 1Ou, 250 x 10 mm, H2O/CH3CN/TFA (92/8/0.1), 4 mL/min, Compound YC-VI-54 eluting at 11 min) to afford 0.035 g (57percent) of compound YC-VI- 54. 1H NMR (400 MHz, D2O) 54.17-4.21 (m, IH), 4.10-4.13 (m, IH), 4.00 (s, 2H), 3.67-3.71 (m, 6H), 3.14-3.20 (m, 4H), 2.43-2.46 (m, 2H), 2.08-2.13 (m, IH), 1.87-1.93 (m, IH), 1.76-1.79 (m, IH), 1.63-1.67 (m, IH), 1.45-1.50 (m, 2H), 1.33-1.40 (m, 2H). ESI-Mass calcd for Ci8H33N4Oi0 [M]+ 465.2, found 465.2.
  • 16
  • [ 501-53-1 ]
  • [ 108466-89-3 ]
  • [ 1254054-91-5 ]
  • 17
  • [ 108466-89-3 ]
  • [ 1207457-31-5 ]
  • 18
  • [ 108466-89-3 ]
  • [ 1207457-32-6 ]
  • 19
  • [ 108466-89-3 ]
  • [ 1207457-33-7 ]
  • 20
  • [ 108466-89-3 ]
  • [ 543-27-1 ]
  • C16H29NO8 [ No CAS ]
  • 21
  • [ 1068148-44-6 ]
  • [ 108466-89-3 ]
  • C47H66N6O10 [ No CAS ]
YieldReaction ConditionsOperation in experiment
N-Boc-8-amino-3,6-dioxaoctanoic acid .x. dicyclohexylamine (300 mg) was dissolved in dimethoxyethane (10 mL). The amine was precipitated by addition of 37percent hydrochloric acid (60 muL) and removed by filtration. Removal of the solvent in vacuo yielded a yellow oil (200 mg, 0.76 mmol) which was dissolved in anhydrous DCM (3 mL). CDI (148 mg, 0.91 mmol) was added and the mixture was allowed to stand at rt for 30 min. DCM (15 mL), 30 (478 mg, 0.76 mmol) and NEt3 (77 mg, 105 muL, 0.76 mmol) were added and the mixture was kept under stirring at rt for 20 h. TFA (10 mL) was added, the mixture was allowed to stand at rt for 4 h before it was concentrated under reduced pressure. MeOH (20 mL) was added twice each time followed by evaporation under reduced pressure. Purification by preparative HPLC (isocratic: MeCN/0.1percent aq TFA 32:68, tR = 14 min) afforded the product as a white fluffy, hygroscopic solid (300 mg, 47percent). inlMMLBox +6.2 cm3 g-1 dm-1 (c 0.010 in MeCN/H2O 9:1); IR (neat): 1670, 1635, 1515, 1495, 1200, 1130 cm-1; 1H NMR (300 MHz, DMSO-d6): delta (ppm) 1.32-1.61 (m, 3H), 1.68 (m, 1H), 2.98 (m, 2H), 3.25 (m, 2H), 3.61 (m, 4H), 3.71 (m, 2H), 4.1 (dd, 1H, 2J = 15.4 Hz, 3J = 6.1 Hz), 4.18 (dd, 1H, 2J = 15.4 Hz, 3J = 6.2 Hz), 4.23 (s, 2H), 4.33 (m, 1H), 5.13 (s, 1H), 6.67 (m, 2H), 7.0 (m, 2H), 7.18-7.33 (m, 10H), 7.8 (br s, 3H), 8.39 (t, 1H, 3J = 5.8 Hz), 8.51 (d, 1H, 3J = 8.1 Hz), 8.81 (s, 2H), 9.12 (m, 1H), 9.32 (s, 1H), 10.98 (s, 1H); 13C NMR (150 MHz, MeOH-d4): delta (ppm) 25.4, 30.2, 40.6, 42.0, 43.7, 54.3, 58.7, 67.9, 71.1, 71.3, 72.1, 116.3, 117.3 (TFA), 119.2 (TFA), 128.1, 128.2, 129.49, 129.52, 129.8, 129.9, 130.0, 130.3, 140.8, 140.9, 154.7, 157.8, 162.7 (TFA), 163.0 (TFA), 163.2 (TFA), 163.4 (TFA), 173.3, 174.0, 174.9; MS (ES, acetonitrile/TFA): m/z 310 [M+2H]2+, 619 [M+H]+; HRMS: (LSI-MS): m/z [M+H]+ calcd for inlMMLBox: 619.3244, found: 619.3257; C33H42N6O6 .x. C4H2F6O4 (846.8).
  • 22
  • [ 560088-79-1 ]
  • [ 108466-89-3 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In 1,2-dimethoxyethane; water; N-Boc-8-amino-3,6-dioxaoctanoic acid × dicyclohexylamine (300 mg) was dissolved in dimethoxyethane (10 mL). The amine was precipitated by addition of 37% hydrochloric acid (?60 muL) and removed by filtration. Removal of the solvent in vacuo yielded a yellow oil (200 mg, 0.76 mmol) which was dissolved in anhydrous DCM (3 mL). CDI (148 mg, 0.91 mmol) was added and the mixture was allowed to stand at rt for 30 min. DCM (15 mL), 30 (478 mg, 0.76 mmol) and NEt3 (77 mg, 105 muL, 0.76 mmol) were added and the mixture was kept under stirring at rt for 20 h. TFA (10 mL) was added, the mixture was allowed to stand at rt for 4 h before it was concentrated under reduced pressure. MeOH (20 mL) was added twice each time followed by evaporation under reduced pressure. Purification by preparative HPLC (isocratic: MeCN/0.1% aq TFA 32:68, tR = 14 min) afforded the product as a white fluffy, hygroscopic solid (300 mg, 47%). inlMMLBox +6.2 cm3 g-1 dm-1 (c 0.010 in MeCN/H2O 9:1); IR (neat): 1670, 1635, 1515, 1495, 1200, 1130 cm-1; 1H NMR (300 MHz, DMSO-d6): delta (ppm) 1.32-1.61 (m, 3H), 1.68 (m, 1H), 2.98 (m, 2H), 3.25 (m, 2H), 3.61 (m, 4H), 3.71 (m, 2H), 4.1 (dd, 1H, 2J = 15.4 Hz, 3J = 6.1 Hz), 4.18 (dd, 1H, 2J = 15.4 Hz, 3J = 6.2 Hz), 4.23 (s, 2H), 4.33 (m, 1H), 5.13 (s, 1H), 6.67 (m, 2H), 7.0 (m, 2H), 7.18-7.33 (m, 10H), 7.8 (br s, 3H), 8.39 (t, 1H, 3J = 5.8 Hz), 8.51 (d, 1H, 3J = 8.1 Hz), 8.81 (s, 2H), 9.12 (m, 1H), 9.32 (s, 1H), 10.98 (s, 1H); 13C NMR (150 MHz, MeOH-d4): delta (ppm) 25.4, 30.2, 40.6, 42.0, 43.7, 54.3, 58.7, 67.9, 71.1, 71.3, 72.1, 116.3, 117.3 (TFA), 119.2 (TFA), 128.1, 128.2, 129.49, 129.52, 129.8, 129.9, 130.0, 130.3, 140.8, 140.9, 154.7, 157.8, 162.7 (TFA), 163.0 (TFA), 163.2 (TFA), 163.4 (TFA), 173.3, 174.0, 174.9; MS (ES, acetonitrile/TFA): m/z 310 [M+2H]2+, 619 [M+H]+; HRMS: (LSI-MS): m/z [M+H]+ calcd for inlMMLBox: 619.3244, found: 619.3257; C33H42N6O6 × C4H2F6O4 (846.8).
  • 23
  • [ 108466-89-3 ]
  • (R)-Nω-(8-amino-3,6-dioxaoctanoyl)-Nα-(2,2-diphenylacetyl)-N-(4-hydroxybenzyl)argininamide bis(hydrotrifluoroacetate) [ No CAS ]
  • 24
  • [ 108466-89-3 ]
  • [ 1310327-56-0 ]
  • 25
  • [ 108466-89-3 ]
  • [ 1310327-62-8 ]
  • 26
  • [ 108466-89-3 ]
  • [ 1351946-91-2 ]
  • [ 1351946-96-7 ]
YieldReaction ConditionsOperation in experiment
28% Preparation 18tert-butyl [2-(2-{2-[(3-{5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-3-yl}propyl)amino]-2-oxoethoxy}ethoxy)ethyl]carbamateThe title compound was prepared by the general method described above for preparation 13, using [2-(2-tert-Butoxycarbonylamino-ethoxy)-ethoxy]-acetic acid (prepared as described in Angew. Chemie Int. Ed. (2006), 45(30), 4936-4940) instead of trans-4-tert-butoxycarbonyl-cyclohexane carboxylic acid, to yield a colourless gum (60 mg, 28percent).1H NMR (400 MHz, CDCl3) delta=1.42 (s, 9H), 1.67-1.98 (m, 7H), 2.14-2.23 (m, 4H), 2.27-2.33 (q, H), 2.64-2.68 (m, 2H), 3.04-3.09 (t, H), 3.21-3.26 (m, H), 3.29-3.37 (m, 3H), 3.53-3.56 (t, 2H), 3.62-3.68 (m, 4H), 3.98 (s, 2H), 4.99 (brm, H), 6.88 (brm, H), 7.53 (t, H), 8.33 (d, H), 8.35 (d, H).MS, m/z=465 ES+ [M+H]+, 465 Cl [M+H]+
  • 27
  • [ 108466-89-3 ]
  • [ 1351947-14-2 ]
  • [ 1351947-13-1 ]
YieldReaction ConditionsOperation in experiment
43% Preparation 36tert-butyl {2-[2-(2-[2-({5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-3-yl}oxy)ethyl]amino}-2-oxoethoxy)ethoxy]ethyl}carbamateThe title compound was prepared by the general method described above for preparation 35, using [2-(2-tert-Butoxycarbonylamino-ethoxy)-ethoxy]-acetic acid (prepared as described in Angew. Chemie Int. Ed. (2006), 45(30), 4936-4940) instead of trans-4-tert-butoxycarbonyl-cyclohexane carboxylic acid, to yield a pale yellow gum (50 mg, 43percent).1H NMR (400 MHz, CDCl3) delta=1.41 (s, 9H), 1.72-1.81 (m, 1H), 1.84-2.01 (m, 2H), 2.18 (s, 3H), 2.21-2.30 (m, 1H), 2.33-2.40 (q, 1H), 3.16-3.26 (m, 4H), 3.50-3.52 (t, 2H), 3.62-3.69 (m, 6H), 4.01 (s, 2H), 4.16-4.19 (t, 2H), 7.44-7.45 (m, 1H), 8.10 (d, 1H), 8.15-8.16 (d, 1H).MS m/z=467 ES+ [M+H]+, 467 Cl [M+H]+
  • 28
  • 2-(2-((tert-butyldiphenylsilyl)oxy)ethoxy)ethanamine 2,2,2-trifluoroacetate [ No CAS ]
  • [ 108466-89-3 ]
  • [ 1365253-82-2 ]
  • 29
  • [ 108466-89-3 ]
  • [ 1365253-91-3 ]
  • 30
  • [ 108466-89-3 ]
  • [ 1365253-84-4 ]
  • 31
  • [ 108466-89-3 ]
  • benzyl 3-(3-(((14-amino-7-oxo-3,9,12-trioxa-6-azatetradecyl)oxy)sulfonyl)benzamido)propanoate 2,2,2-trifluoroacetate [ No CAS ]
  • 32
  • [ 108466-89-3 ]
  • 10-(1-(((3-((3-(benzyloxy)-3-oxopropyl)carbamoyl)phenyl)sulfonyl)oxy)-7,16-dioxo-3,9,12-trioxa-6,15-diazaoctadecan-18-yl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide [ No CAS ]
  • 33
  • [ 108466-89-3 ]
  • 10-(1-(((3-((2-carboxyethyl)carbamoyl)phenyl)sulfonyl)oxy)-7,16-dioxo-3,9,12-trioxa-6,15-diazaoctadecan-18-yl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide [ No CAS ]
  • 34
  • [ 1346128-86-6 ]
  • [ 108466-89-3 ]
  • [ 1346128-87-7 ]
  • 35
  • [ 1045709-90-7 ]
  • [ 108466-89-3 ]
  • [ 1246261-24-4 ]
 

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