4-(1-Aminoethyl)aniline hydrochloride synthesis

Yield:-

Reaction Conditions:

with hydrogenchloride;hydrogen;palladium 10% on activated carbon in ethanol;water; under 760.051 Torr;

Steps:

48

First step, hydroxyamine hydrochloride (4.18 g) and NaOAc (9.93 g) were added to a solution of p-aminoacetophenone (5 g) in EtOH (80 ml). The reaction mixture was stirred at 60°C for 6 h. EtOH was removed under reduced pressure. H₂O (40 ml) was added to the residue, and extracted with EtOAc (3 × 40 ml). The EtOAc of the combined organic layer was removed by rotary evaporation under reduced pressure to yield p-aminoacetophenone oxime (5.56 g) as a pale yellowish solid. Second step, a solution of p-aminoacetophenone oxime (5.56 g) and concentrated HCl (20 ml) in EtOH (50 ml) was subjected to hydrogenation at atmospheric pressure in the presence of 10% Pd/C (784 mg). The reaction solution was filtered and the filtrate was concentrated to yield 1-(p-aminophenyl)-ethylamine hydrochloride (7.5 g) as a white solid. Third step, a mixture of 1-(p-aminophenyl)-ethylamine (363 mg, the hydrochloride), 6-chloropurine riboside (200 mg) and triethylamine (3 ml) in PrOH (60 ml) was heated to 70°C for 8h. After evaporation of the reaction mixture, the residue was separated by column chromatography over silica gel and eluted with CHCl₃-CH₃OH (20 : 1) to yield N⁶-[(+/-)-1-(4-aminophenyl)-ethyl] -adenosine(220 mg) as a white solid: positive ESIMS m/z 387 [M + H]⁺ and 409 [M + Na]⁺; negative ESIMS m/z 385 [M - H]^- and 421 [M + Cl]^-; ¹H NMR (300 MHz, DMSO-d₆): the adenosine moiety δ 8.34 (1H, s, H-2), 8.15 (1H, s, H-8), 8.00 (1H, d, J= 8.4 Hz, -NH), 5.86 (1H, d, J= 5.7 Hz, H-1), 5.40 (2H, m, 2×-OH), 5.15 (1H, d, J= 4.5Hz, -OH), 4.58 (1H, m, H-2'), 4.12 (1H, m, H-3'), 3.94 (1H, m, H-4'), 3.66 (1H, m, H-5'a), 353 (1H, m, H-5'b); the (+/-)-1-(4-aminophenyl)-ethyl moiety δ 7.08 (2H, d, J = 8.4 Hz, H-2", H-6"), 6.46 (1H, d, J = 8.4 Hz, H-3", H-5"), 5.43 (1H, m, H-7"), 4.88 (1H, brs, -NH₂), 1.46 (1H, d, J = 6.9 Hz, H-8"); ¹³CNMR (75MHz, DMSO-d₆): the adenosine moiety δ 153.9 (s, C-6), 152.4 (d, C-2), 148.5 (s, C-4), 139.7 (d, C-8), 119.8 (s, C-5), 88.0 (d, C-1), 86.0 (d, C-4), 73.6 (d, C-2), 70.8 (d, C-3), 61.8 (t, C-5'); the (+/-)-1-(4-aminophenyl)-ethyl moiety δ 147.4 (s, C-4"), 132.1 (s, C-1), 127.0 (d, C-2, C-6), 113.7 (d, C-3, C-5), 48.2 (d, C-7), 22.4 (q, C-8")o Example 49: preparation of N⁶-{(+)-1-[4-(2-methyl-propyl)-phenyl]-ethyl}-adenosine

References:

EP2511283,2012,A1 Location in patent:Page/Page column 64