2-[2-(2-Aminoethoxy)ethoxy]ethanol

NH2-PEG3 (PROTAC Linker 35) is a PROTAC linker, which belongs to a polyethylene glycol (PEG) linker. NH2-PEG3 (PROTAC Linker 35) can be used in the synthesis of the PROTAC (β-NF-JQ1)[1].

2-(2-(2-azidoethoxy)ethoxy)ethanol (0.7 g, 3.99 mmol) was dissolved in MeOH (9 ml), then palladium on activated carbon (0.196 g) was added under stirring. The flask was submitted to 3 evacuation/HThe azide was combined with Pd/C (150 mg) in MeOH (8.0 ml_) and stirred 12 h under HPreparation of Compound 20f Pd/C (10 wt. percent, 1.0 g) was added to a solution of compound 2a (6.7 g, 38.2 mmol) in MeOH (38 mL). After stirring at room temperature for 8 hours under hydrogen, the reaction mixture was filtered through a celite pad and washed with MeOH (100 mL). Concentration provided compound 20f (5.6 g, 99 percent) as colorless oil, which was used without further purification. 1H- MR (400 MHz, CDC1Pd/C (10 wt. percent, 1.0 g) was added to a solution of compound 2a (6.7 g, 38.2 mmol) in MeOH (38 mL). After stirring at room temperature for 8 hours under hydrogen, the reaction mixture was filtered through a celite pad and washed with MeOH (100 mL). (0985) Concentration provided compound 20f (5.6 g, 99 percent) as colorless oil, which was used without further purification. 1H-NMR (400 MHz, CDC1Triphenylphosphine (9.89 g, 37.70 mmol) was added to a solution of compound 2 (4.40 g, 25.10 mmol) in THF (20 mL) and water (10 mL), and the mixture was stirred for 12 h at 45 °C. The solvents were evaporated under reduced pressure at 40 °C, and the residue was dissolved with slightly acidic water with pH 5-6 by using 10percent KHSOGeneral procedure: Compound 6a (1.00 g, 5.27 mmol), and a catalytic amount of 5 percent Pd/C were dissolved in anhydrous methanol (30 mL) and the reaction mixture was stirred at 24  for 1.5 h under HThe above synthesized azide 3 (1.27 g, 7.25 mmol) was dissolved in MeOH (15 mL). Pd/C (0.22 g, 0.03 mmol) was added, the flask was purged of argon and filled with hydrogen. The solution was stirred overnight at room temperature. The mixture was filtered through celite and the solvent was evaporated to yield the pure amino alcohol 4 (1.03 g, 95percent). 4: Light yellow oil; The synthesis was done according to literature under argon.[1] The crude educt 1 (6.00 g, 34.4mmol) was dissolved in THF (50 mL) and triphenylphosphine (11.7 g, 44.7 mmol) was added in two portions. After stirring for 48 h at room temperature, water (1.13 mL) was added and stirring was continued for another 48 h. The solvent was removed under reduced pressure and the residue is afterwards dried under high vacuum at 45 °C overnight. Water (119 mL) was added and the formed precipitate is removed by filtration. After washing the solid with water(200 mL), the solvent was evaporated under reduced pressure and the product was dried inhigh vacuum at 70 °C overnight.2-[2-(2-Chloroethoxy)ethoxy]ethanol (4, 6.3 g, 37 mmol), NaI (1.8 g, 12 mmol), and NaN3 (3.9 g, 60 mmol) were dissolved in 30 mL of deionized water and then stirred at 60 °C for 16 h. The reaction mixture was filtered to remove insoluble matter. The filtered solution was extracted with 60 mL of EtOAc. The organic layer was dried over Na2SO4 and evaporated to yield the azide (6.5 g). The azide (6.5 g) was dissolved in MeOH containing 0.5 g of 5percent Pd–C and was stirred under a hydrogen atmosphere at room temperature for 12 h. The reaction mixture was filtered using Celite and was evaporated to yield the corresponding amine (6.2 g). The amine was dissolved in150 mL of CH3CN. This was followed by the addition of 30 mL of deionized water, 30 mL of 1 M NaOH, and (Boc)2O (8.1 g, 37 mmol) at room temperature for16 h. The reaction mixture was evaporated and the resultant residue was added to 100 mL of water and then extracted with an equal volume of EtOAc. The organic layer was dried over Na2SO4. After evaporation of the organic layer, the residue that was obtained was purified by silica gel column chromatography (200 g, MeOH-CHCl3 1/50) to yield 5 (6.2 g, 25 mmol) as acolorless oil. The yield from the three steps was 68percent. 1H NMR (270 MHz, CDCl3): 5.21 (1H, br. s), 3.68(2H, t, J = 7.1 Hz), 3.61–3.52 (6H, m), 3.50 (2H, t, J = 7.1 Hz), 3.24 (2H, t, J = 6.9 Hz), 2.88 (1H, br. s), 1.37 (9H, s); 13C NMR (67.8 MHz, CDCl3): 155.9, 79.1, 72.5, 72.4, 70.2, 70.1, 61.5, 40.3, 28.2; FD-MSm/z (rel.int.): 250 (100, [M + H]+), 249 (13.0, [M]+), 57.0 (25.1), 31.0 (16.1); FD-HR-MS m/z: calcd. forC11H24NO5, 250.16545, found 250.16572.To a 1L hydrogenation reactor were added 29g BP103a02, methanol 360 mL, palladium on carbon 5.0g, and stirred. Nitrogen was replaced, and hydrogen was introduced to react for 3-4h. After the completion of the reaction under the monitor of TLC, the reaction liquid was filtered, and the filtrate was concentrated to give 23.5g BP103a03 as an oil.Using a 10percent Pd/C cartridge, a 0.05 M solution of 8-dibenzylamino-3, 6-dioxaoctan-1-ol (1.00 g, 3.04 mmol) in absolute ethanol (60 mL) was cycled twice through an H-CubeCompound 15 (3.7 g, 17.36 mmol) was dissolved in 30 mL of aqueous ammonia and stirred at 70 ° C for 24 h.After the reaction was completed, the solvent was spun off and 15 mL of water was added. The mixture was washed with dichloromethane (3 * 20 mL) and dried over anhydrous sodium sulfate. After the organic solvent was removed, 2.4 g of compound 16 was obtained with a yield of 93percent

Molecular Weight:149.19
XLogP3:-1.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:7
Exact Mass:149.10519334
Monoisotopic Mass:149.10519334
Topological Polar Surface Area:64.7
Heavy Atom Count:10
Complexity:61
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes