4-[2-(dimethylamino)ethoxy]aniline

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 5-chloropyrazolo[1,5-a]pyrimidine-3-carbaldehyde (50 mg, 0.276 mmol) in dioxane was added 4-(2-(dimethylamino)ethoxy)aniline (149 mg, 0.829 mmol). The mixture was heated in microwave 100 minutes at 120° C. Water and dichloromethane were added, and the product was extracted into dichloromethane. The organic layer was dried over Na2SO4 and concentrated under reduced pressured to yield 5-(4-(2-(dimethylamino)ethoxy)phenylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde. LCMS (M+1=408) the product was extracted into dichloromethane The organic layer was dried over Na2SO4 concentrated under reduced pressured

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of 4-[2-(dimethylamino)ethoxy]aniline [R Paul et al, J. Med. Chem. 36, 1993, 2716-2725](3.61 g, 20 mmol) in water (34 mL) and concentrated HCl (10 mL) was diazotized at 0° C. with a solution of NaNO2 (1.52 g, 22 mmol) in water (4 mL). The cold solution was added in one portion to a vigorously stirred ice-cold mixture of ethyl 2-methylacetoacetate (3.03 g, 21 mmol), anhydrous NaOAc (17 g), EtOH (25 mL), and freshly added ice (20 g). After stirring at 20° C. for 1 h, the mixture was cooled to 0° C., basified by the slow addition of solid Na2CO3, and extracted immediately with CH2Cl2 (×2). The combined organic layers were washed with water, dried (Na2SO4), and evaporated. The residue was extracted with hot petroleum ether (bp 60-65° C.) in the presence of decolorizing charcoal, and the clarified solution was evaporated. The remaining oil (4.55 g) was dissolved in absolute EtOH (6 mL) and HCl-saturated EtOH (10 mL) was added. After heating at reflux for 25 min, the solution was concentrated and the residue was partitioned between dilute Na2CO3 and CH2Cl2. The organic layer was washed with water and NaCl solution, dried, and evaporated. The residue was triturated with iPr2O/hexanes and the resulting solid was recrystallized from iPr2O/hexanes to give ethyl 5-[2-(dimethylamino)ethoxy]indole-2-carboxylate (1.32 g, 24% overall yield) as needles, mp 110° C. 1H NMR [(CD3)2SO] δ 11.72 (s, 1 H, NH), 7.34 (d, J=9.0 Hz, 1 H, H-7), 712 (d, J=2.4 Hz, 1 H, H-4), 7.03 (d, J=1.6 Hz, 1 H, H-3), 6.91 (dd, J=9.0, 2.4 Hz, 1 H, H-6), 4.32 (q, J=7.1 Hz, 2 H, CH2CH3), 4.03 (t, J=5.9 Hz, 2 H, OCH2), 2.63 (t, J=5.9 Hz, 2 H, OCH2CH2), 2.22 (s, 6 H, N(CH3)2), 1.33 (t, J=7.1 Hz, 3 H, CH2CH3). the mixture was cooled to 0° C. extracted immediately with CH2Cl2 (×2) The combined organic layers were washed with water dried (Na2SO4) evaporated The residue was extracted with hot petroleum ether (bp 60-65° C.) in the presence of decolorizing charcoal the clarified solution was evaporated The remaining oil (4.55 g) was dissolved in absolute EtOH (6 mL) HCl-saturated EtOH (10 mL) was added After heating at reflux for 25 min the solution was concentrated the residue was partitioned between dilute Na2CO3 and CH2Cl2 The organic layer was washed with water and NaCl solution dried evaporated The residue was triturated with iPr2O/hexanes the resulting solid was recrystallized from iPr2O/hexanes

反応条件: temp:0.00; pressure:0.00; stir: