N-methyldodecan-1-amine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of N-methyl-N-dodecylamine (2.5 ml) and triethylamine (1.4 ml) in dichloromethane (10 ml) was added with stirring and ice cooling a solution of bromoacetyl bromide (0.87 ml) in dichloromethane (10 ml). The cooling bath was removed after 30 min and the reaction stood for 16 h at ambient temperature. The mixture was washed with water and saturated sodium hydrogen carbonate, dried (K2CO3) and the solution purified by flash chromatography (silica, methanol-dichloromethane). Appropriate fractions were combined and evaporated to a pale yellow oil, yield 1.53 g (48%). 1H-NMR (CDCl3) δ0.8 (3H,t), 1.2 (18H,m), 1.5 (2H,m,), 2.88 and 2.99 (3H,2xs), 3.27 (2H,m), 3.77 and 3.79 (2H,s)); MS (APCI+) found (M+1)=320, 322, C15H30BrNO requires 319,321. The cooling bath was removed after 30 min The mixture was washed with water and saturated sodium hydrogen carbonate dried (K2CO3) the solution purified by flash chromatography (silica, methanol-dichloromethane) evaporated to a pale yellow oil, yield 1.53 g (48%)

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

Procedure: The same procedure as employed in the preparation of Example 5, step d, but using 4-({[ethoxy(oxo)acetyl][4-(trifluoromethyl)benzyl]amino}methyl)benzoic acid and dodecyl-methyl-amine gave the title compound as a colorless oil (56%). HPLC (Condition A), Rt: 7.41 min (HPLC purity: 82%). The same procedure as employed in the preparation of Example 5, step d

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

Procedure: To a solution of N-methyl-N-dodecylamine (2.5 ml) and triethylamine (1.4 ml) in dichloromethane (10 ml) was added with stirring and ice cooling a solution of bromoacetyl bromide (0.87 ml) in dichloromethane (10 ml). The cooling bath was removed after 30 min and the reaction stood for 16 h at ambient temperature. The mixture was washed with water and saturated sodium hydrogen carbonate, dried (K2CO3) and the solution purified by flash chromatography (silica, methanol-dichloromethane). Appropriate fractions were combined and evaporated to a pale yellow oil, yield 1.53 g (48%). 1H-NMR (CDCl3) δ0.8 (3H,t), 1.2 (18H,m), 1.5 (2H,m,), 2.88 and 2.99 (3H,2xs), 3.27 (2H,m), 3.77 and 3.79 (2H,s)); MS (APCI+) found (M+1)=320, 322, C15H30BrNO requires 319,321. The cooling bath was removed after 30 min The mixture was washed with water and saturated sodium hydrogen carbonate dried (K2CO3) the solution purified by flash chromatography (silica, methanol-dichloromethane) evaporated to a pale yellow oil, yield 1.53 g (48%)

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

Procedure: To a solution of N-methyl-N-dodecylamine (2.5 ml) and triethylamine (1.4 ml) in dichloromethane (10 ml) was added with stirring and ice cooling a solution of bromoacetyl bromide (0.87 ml) in dichloromethane (10 ml). The cooling bath was removed after 30 min and the reaction stood for 16 h at ambient temperature. The mixture was washed with water and saturated sodium hydrogen carbonate, dried (K2CO3) and the solution purified by flash chromatography (silica, methanol-dichloromethane). Appropriate fractions were combined and evaporated to a pale yellow oil, yield 1.53 g (48%). 1H-NMR (CDCl3) δ0.8 (3H,t), 1.2 (18H,m), 1.5 (2H,m,), 2.88 and 2.99 (3H,2xs), 3.27 (2H,m), 3.77 and 3.79 (2H,s)); MS (APCI+) found (M+1)=320, 322, C15H30BrNO requires 319,321. The cooling bath was removed after 30 min The mixture was washed with water and saturated sodium hydrogen carbonate dried (K2CO3) the solution purified by flash chromatography (silica, methanol-dichloromethane) evaporated to a pale yellow oil, yield 1.53 g (48%)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a stirred ice cold solution of N-methyldodecanamine (5.0 g, 25.1 mmol) and DIEA (5.70 mL, 1.3 equiv, 32.6 mmol) in anhydrous DCM (150 mL) was added 3-azido-3-methylbutanoyl chloride (4.05 g, 1 equiv, 25.1 mmol) in small portions. The ice bath was removed and the reaction was stirred and left at room temperature for 3 h. The content of the reaction was poured into a separatory funnel. The organic layer was washed with 1 M HCl (3×100 mL) and saturated NaHCO3 (2×100 mL). It was dried over anhydrous MgSO4, filtered, concentrated and dried under high vacuum to give a crude oil (8.08 g, quant). This material was purified on an ISCO flash chromatography system with a gradient from 10-40% ethyl acetate and hexanes as eluent. The desired fractions were collected and concentrated to give a pale yellow oil (7.28 g, 89.3%). 1H NMR (CDCl3, 400 MHz): δ 0.88-0.94 (m, 3H), 1.26-1.35 (m, 6H), 1.47-1.48 (d, J=4, 6H), 1.50-1.59 (m, 2H), 2.51 (s, 2H), 2.94-3.04 (d, J=40, 3H), 3.30-3.40 (m, 2H). LRMS (ESI+) for C18H36N4O (324.3); Found: 325 (MH+). The ice bath was removed The content of the reaction was poured into a separatory funnel The organic layer was washed with 1 M HCl (3×100 mL) and saturated NaHCO3 (2×100 mL) It was dried over anhydrous MgSO4 filtered concentrated dried under high vacuum to give a crude oil (8.08 g, quant) This material was purified on an ISCO flash chromatography system with a gradient from 10-40% ethyl acetate and hexanes as eluent The desired fractions were collected concentrated

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

Procedure: The same procedure as employed in the preparation of Example 5, step d, but using 4-({[ethoxy(oxo)acetyl][4-(trifluoromethyl)benzyl]amino}methyl)benzoic acid and dodecyl-methyl-amine gave the title compound as a colorless oil (56%). HPLC (Condition A), Rt: 7.41 min (HPLC purity: 82%). The same procedure as employed in the preparation of Example 5, step d

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

Procedure: To a solution of N-methyl-N-dodecylamine (2.5 ml) and triethylamine (1.4 ml) in dichloromethane (10 ml) was added with stirring and ice cooling a solution of bromoacetyl bromide (0.87 ml) in dichloromethane (10 ml). The cooling bath was removed after 30 min and the reaction stood for 16 h at ambient temperature. The mixture was washed with water and saturated sodium hydrogen carbonate, dried (K2CO3) and the solution purified by flash chromatography (silica, methanol-dichloromethane). Appropriate fractions were combined and evaporated to a pale yellow oil, yield 1.53 g (48%). 1H-NMR (CDCl3) δ0.8 (3H,t), 1.2 (18H,m), 1.5 (2H,m,), 2.88 and 2.99 (3H,2xs), 3.27 (2H,m), 3.77 and 3.79 (2H,s)); MS (APCI+) found (M+1)=320, 322, C15H30BrNO requires 319,321. The cooling bath was removed after 30 min The mixture was washed with water and saturated sodium hydrogen carbonate dried (K2CO3) the solution purified by flash chromatography (silica, methanol-dichloromethane) evaporated to a pale yellow oil, yield 1.53 g (48%)

Conditions: temp:0.00; pressure:0.00; stir: