N-(3-Methoxy-3-oxopropyl)-N-(phenylmethyl)-β-alanine methyl ester

A solution of benzylamine (10.7 g, 0.1 mol) in MeOH (50 mL) was added in dropwise to a solution of methyl acrylate (18.9 g, .022 mol) in MeOH (100 mL) at rt. The result mixture was refluxed for 8h, and evaporated in vacuum to give 27.9 g product in quantitative yield. ‘H-NIVIR (400 MHz, CDC13) : 7.28 (m., 5H), 3.64 (s, 2H), 3.59 (s, 6H), 2.80 (m, 4H), 2.47 (m, 4H).The preparation of dendrimer 6 was carried out using a methodreported in the literature [19] and modified according to ourneeds. In particular, product 3 ( Fig. 1) was prepared startingfrom a solution of benzylamine 1 (0.88mL; 8 mmol) in methanol(20mL) to whichmethylacrylate 2 (2.6 mL; 28.8 mmol) was addedin a dropwise fashion. The resulting reaction mixture was stirredunder argon for 72 h at 34°C. After this time, the solvent was removedunder reduced pressure and the residue obtained confirmedto be pure 3 via 1H NMR and was used in the following stepwithout further purificationExample 7a At room temperature, to a 500mL three-necked bottle, 18.9g (0.22ml) of methyl acrylate and 100mL of methanol were added, and a mixture solution of 10.7g (0.1mol) of benzylamine and 50mL of methanol was slowly added dropwise to the three-necked bottle under stirring. The temperature was naturally elevated, and the addition rate was controlled so that the temperature of reaction system was not greater than 50°C. After the addition, the reaction was stirred at room temperature for 0.5h, and reacted for 8 h under reflux. After completion of the reaction, the unreacted methanol and methyl acrylate were removed by vacuum distillation to obtain light yellow oily product N, N-bis(β-methoxy carbonylethyl) benzylamine, 27.3g, yield 98percent, bp 174-176°C/533Pa.At room temperature, to a 500 mL three-necked bottle, 18.9 g (0.22 mol) of methyl acrylate and 100 mL of methanol were added, and a mixture solution of 10.7 g (0.1 mol) of benzylamine and 50 mL of methanol was slowly added dropwise to the three-necked bottle under stirring. To a 250 ml three-necked reaction flask equipped with a mechanical stirrer, a condenser, and a thermometer, 43 g (0.5 mol) of methyl acrylate and 32 g (40 ml) of methyl acrylate were added and 21.4 g (0.2 mol) of benzylamine was added under stirring. The reaction was stirred for 7 hours .After completion of the reaction, excess methyl acrylate and methanol were recovered, and the water pump was distilled under reduced pressure to an inner temperature of 100 to 110 ° C to obtain 54 g of crude product (C) as a yellow oily substance in a yield of 97percent and an amount of 94.3percent.[Synthesis of a linker compound] A linker compound of the present invention was synthesized according to the following procedure. As shown in following general formula (10), benzylamine (Compound 1, Bn represents a benzyl group in the formula) was brought into reaction with methyl acrylate (6 equiv.) in methanol (in the formula, MeOH) at room temperature. Two units of methyl acrylate were added by Michael addition to the benzylamine to obtain Compound 2 at the yield of 93percent. Thereafter, a large excess (50 equiv.) of ethylenediamine was added into methanol containing Compound 2 at room temperature. The ethylenediamine was condensed with Compound 2 to obtain Compound 3. It is to be noted that a large excess (50 equiv.) of ethylenediamine is added in order to prevent Compound 2 from condensing simultaneously with two amino groups of ethylenediamine. [] Compound 2 was obtained by the following procedure. A methanol solution (143 mL) of benzylamine (4.7 mL, 44.6 mmol) was mixed with methyl acrylate (8.52 mL, 104 mmol), stirred for 8 hours under nitrogen atmosphere at room temperature, further mixed with methyl acrylate (3.87 mL, 47 mmol), and stirred at room temperature for 12 hours. Thereafter, the stirred solution was further mixed with methyl acrylate (7047 mL, 94 mmol) and stirred overnight to obtain a reaction solution of methanol and methyl acrylate. The methanol/methyl acrylate reaction solution was concentrated under reduced pressure to obtain a residue. The residue was purified by medium-pressure silica gel chromatography (300 g, toluene:ethyl acetate=5:1 to 3:1) to obtain a colorless oily solution serving as Compound 2. Compound 2 was obtained at the yield of 11.7 g (95percent). Also, 1H NMR (400 MHz, CD3OD) measurement was conducted on Compound 2 so obtained to find that δ7.28-7.20 (5H, m, aromatic), δ4.79 (6H, s, OMe*.x.2), δ3.57 (2H, d, J=4.6 Hz, NCH2*Ph), δ2.76 (4H, td, Jgem=4.6, Jvic=6.8 Hz , CH2*NBn), δ2.46 (4H, td, Jgem=4.6, Jvic=6.8 Hz, COCH2*CH2NBn). It is to be noted that each chemical shift δ indicates a measured value corresponding to a proton having a plurality of Hs marked with *, i.e., H*. The same applies to the following description. An ESI-MS (positive) measurement (time-of-flight mass spectrometer measurement) was conducted to find that the m/z (mass/charge) was 302.1 [(M+Na)+].

Molecular Weight:279.33
XLogP3:1.4
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:10
Exact Mass:279.14705815
Monoisotopic Mass:279.14705815
Topological Polar Surface Area:55.8
Heavy Atom Count:20
Complexity:280
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes