ethyl 2-(2-aminoethoxy)acetate;hydrochloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of hydrogen chloride in 1,4-dioxane (4M, 32.7 ml, 131 mmol) was added to a solution of 2-(2-aminoethoxyl)acetic acid (1.56 g, 13.10 mmol) in ethanol (38.2 ml, 655 mmol) and heated for 2 h at a gentle reflux. The reaction mixture was evaporated to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, br, 3H), 4.18 (s, 2H), 4.17-4.08 (m, 2H), 3.75-3.68 (m, 2H), 2.99-2.90 (m, 2H), 1.20 (t, 3H). heated for 2 h at a gentle reflux The reaction mixture was evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde (intermediate 41, 1.50 g, 5.40 mmol), ethyl 2-(2-aminoethoxyl)acetate hydrochloride (intermediate 105, 1.24 g, 6.75 mmol) and triethylamine (0.97 ml, 7.02 mmol) in 1,2-dichloroethane (25 ml) at room temperature was stirred for 1 h and then sodium triacetoxyborohydride (1.83 g, 8.63 mmol) was added. The reaction mixture was stirred for 18 h at room temperature and additional sodium triacetoxyborohydride (0.92 g, 4.32 mmol) was added. After a further 5 h stirring at room temperature the reaction mixture was partitioned between saturated aqueous NaHCO3 solution and DCM, the mixture extracted with DCM (3×), the combined organic layers dried over Na2SO4 and evaporated. The residue was applied to a 80 g RediSep® silica and purified by normal phase chromatography, eluting with a gradient from DCM to 10% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as an yellow solid. (UPLC-MS 6) tR 0.42; ESI-MS 322.2 [M+H]+. The reaction mixture was stirred for 18 h at room temperature After a further 5 h stirring at room temperature the reaction mixture was partitioned between saturated aqueous NaHCO3 solution and DCM the mixture extracted with DCM (3×) the combined organic layers dried over Na2SO4 evaporated purified by normal phase chromatography eluting with a gradient from DCM to 10% MeOH in DCM Product containing fractions evaporated