2-(2-Methoxyethoxy)-N,N-bis[2-(2-methoxyethoxy)ethyl]ethanamine

CLEAR PALE YELLOW TO BROWN LIQUID

4-phenylamino-5-phenyl-7-(5-deoxy-4-C-methyl-2, 3-O-(methylethylidene)-beta-D-ribofuranosyl)pyrrolo-[2, 3-d]pyrimidine Hexamethylphosphorous triamide (800 muL, 4.35 mmol) was added to a solution of carbon tetrachloride (600 muL, 5.8 mmol) and the compound of (272 mg, 1.45 mmol) in dry toluene at -50° C. The reaction mixture was warmed to -10° C. in the course of 30 minutes and stirred at -10° C. for 15 minutes. The orange solution was quenched with water, diluted with toluene and washed with water and saturated aqueous sodium chloride. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to a volume of c.a. 5 mL. The chloro-sugar solution was added to a mixture of 4-phenylamino-5-phenyl-pyrrolo[2, 3-d]pyrimidine (830 mg, 2.9 mmol), finely powdered potassium hydroxide (85percent, 380 mg, 5.8 mmol) and Tris[2-(2-methoxyethoxy)ethyl]amine (925 muL, 2.9 mmol) in dry toluene which had been stirring at room temperature for 90 minutes. After stirring overnight at room temperature, the reaction mixture was diluted with ethyl acetate and washed with saturated aqueous ammonium chloride. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (hexanes/ethyl acetate 70/30 to 50/50). Yield: 223 mg, 34percent, Rf=0.3 (silica gel, hexanes/ethyl acetate 60/40).Under a nitrogen atmosphere, a 2-chloroethyl methyl ether 14.92 Kg (157.8 mol, 4 eq) was charged into a 50 L stainless steel reactor.Triethanolamine borate 6.2Kg (39.46mol, 1eq), tetrabutylammonium bromide 1.2Kg and dimethyl sulfoxide 28Kg, heated to 60At °C, 7.75Kg (138mol, 3.5eq) of potassium hydroxide was added in batches, and the reaction was carried out by heating to 120 ° C for 5-6 hours.By GC, a yellow oily liquid tris(3, 6-dioxaheptyl)amine 11.01 Kg was obtained by distillation, HNMR purity: 99.4percent, yield: 86.3percent.139 g (1 mol) of 2-bromoethyl methyl ether was placed in the reaction flask.Triethanolamine borate 31.4g (0.2mol), tetrabutylammonium chloride 5.6g (0.02mol) and350 g of sulfolane, heated to 60 ° C, Start adding 32g (0.8mol) of sodium hydroxide in batches.After heating to 120 ° C for 3 to 4 hours, sampling GC detection, By rectification, 59.9 g of tris(3, 6-dioxaheptyl)amine was obtained as a yellow oily liquid.Nuclear magnetic purity: 99.3percent, yield: 92.7percent.(0263) [0231] 2.922 g (0.02 moles) of alpha-ketoglutaric acid was dissolved in 10 mL of dry acetone. A separate solution was made from 12.937 g (0.04 moles) of tris[2-(2-(methoxyethoxy)ethyl] amine (TMEEA) in 5 mL of dry acetone. The amine solution was added dropwise with stirring over the course of 2 minutes to the AKG solution; no visible indication of reaction was seen, but the resulting mixture became slightly warm (approximately 35 - 45° C). The mixture was shaken briefly but vigorously, and cooled in a freezer for 30 minutes. Even when cold, still no precipitation of product occurred, so the acetone was removed via a stream of nitrogen followed by treatment in a vacuum oven at room temperature. This gave a clear, golden-brown colored, slightly viscous oil in quantitative yield.810 mg (1.89 mmol) of a compound (Mw: 428.19) represented by '5a', 3.6 ml (11.34 mmol) of tris [2- (2-methoxy ethoxy) ethyl] amine (Mw: 323.43), 10 ml of CH 3 CN were added to a 30 ml vial tube and after purging with nitrogen, the mixture was stirred at 150 ° C for 3 h using a microwave synthesizer. After the reaction, the reaction solution was evaporated under reduced pressure, then dissolved in water to remove the insoluble components by filtration, and the one that was distilled off under reduced pressure was washed with hexane. Further, this was dissolved in dichloromethane, washed with 1M NaBr aqueous solution, & dried using sodium sulfate, then distillation under reduced pressure, and again washed with hexane to obtain 1.01 g of a brown oily substance. NMR and elemental analysis confirmed the synthesis of [(mee) 3 NC 2 AzoC 2 N (mee) 3] 2+ Br 2 represented by '5b'.To a suspension of 2-amino-4-chloro-1H-pyrrolo[2, 3-d]pyrimidine [Liebigs Ann. Chem. 1: 137 (1983)] (3.03 g, 18 mmol) in anhydrous MeCN (240 mL), powdered KOH (85percent; 4.2 g, 60 mmol) and tris[2-(2-methoxyethoxy)-ethyl]amine (0.66 mL, 2.1 mmol) were added and the mixture was stirred at room temperature for 10 min. Then a solution of 2, 3, 5-tri-O-benzyl-D-arabinofuranosyl bromide [prepared from corresponding 1-O-p-nitrobenzoate (11.43 g, 20.1 mmol) according to Seela et al., J. Org. Chem. (1982), 47, 226] in MeCN (10 mL) was added and stirring continued for another 40 min. Solid was filtered off, washed with MeCN (2*25 mL) and combined filtrate evaporated. The residue was purified on a silica gel column with a solvent system of hexanes/EtOAc: 7/1, 6/1 and 5/1. Two main zones were separated. From the more rapidly migrating zone was isolated the alpha anomer (0.74 g) and from the slower migrating zone the desired 3 anomer (4.01 g).

Molecular Weight:323.43
XLogP3:-0.6
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:18
Exact Mass:323.23078777
Monoisotopic Mass:323.23078777
Topological Polar Surface Area:58.6
Heavy Atom Count:22
Complexity:175
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes