N-(2-chloroethyl)-N-ethylaniline

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Compound 3a (590 mg, 3.2 mmol), K2CO3 (887 mg, 6.4 mmol), KI (106 mg, 0.66 mmol) were mixed in DMF (50 mL). 4-aminophenol (600 mg, 5.4 mmol) was added portionwise, the reaction mixture was heated and stirred at 80° C. for 18 hr. After cooling to room temperature, the solvent was evaporated and the residue was quenched with 100 mL water. The mixture was adjusted pH to ˜7 with diluted hydrochloric acid. The mixture was then extracted with EtOAc and the combined organic layer was washed with water and then brine and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography provide the compound 21 (570 mg, 1.9 mmol, 60% yield) as a pale solid. 1H NMR (CDCl3, 400 MHz) δ 7.39 (d, J=9.2 Hz, 2H), 7.26 (t, J=7.6 Hz, 2H), 6.68-6.87 (m, 5H), 4.10 (t, J=6.0 Hz, 2H), 3.72 (t, J=6.4 Hz, 2H), 3.49 (q, J=7.2, 2H), 2.16 (s, 3H), 1.21 (t, J=7.2 Hz, 3H); HRMS (ESI, positive) m/z calcd. for C18H23N2O2 [M+H]+: 299.17540, found: 299.17538. the reaction mixture was heated After cooling to room temperature the solvent was evaporated the residue was quenched with 100 mL water The mixture was then extracted with EtOAc the combined organic layer was washed with water brine and dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Compound 3a (590 mg, 3.2 mmol), K2CO3 (887 mg, 6.4 mmol), KI (106 mg, 0.66 mmol) were mixed in DMF (50 mL). 4-aminophenol (600 mg, 5.4 mmol) was added portionwise, the reaction mixture was heated and stirred at 80° C. for 18 hr. After cooling to room temperature, the solvent was evaporated and the residue was quenched with 100 mL water. The mixture was adjusted pH to ˜7 with diluted hydrochloric acid. The mixture was then extracted with EtOAc and the combined organic layer was washed with water and then brine and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography provide the compound 21 (570 mg, 1.9 mmol, 60% yield) as a pale solid. 1H NMR (CDCl3, 400 MHz) δ 7.39 (d, J=9.2 Hz, 2H), 7.26 (t, J=7.6 Hz, 2H), 6.68-6.87 (m, 5H), 4.10 (t, J=6.0 Hz, 2H), 3.72 (t, J=6.4 Hz, 2H), 3.49 (q, J=7.2, 2H), 2.16 (s, 3H), 1.21 (t, J=7.2 Hz, 3H); HRMS (ESI, positive) m/z calcd. for C18H23N2O2 [M+H]+: 299.17540, found: 299.17538. the reaction mixture was heated After cooling to room temperature the solvent was evaporated the residue was quenched with 100 mL water The mixture was then extracted with EtOAc the combined organic layer was washed with water brine and dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of compound 3a (500 mg, 2.7 mmol), K2CO3 (750 mg, 5.4 mmol), KI (90 mg, 0.54 mmol) in DMF (50 mL) was bubbled with argon for 10 min Catechol (600 mg, 5.4 mmol) was added to the mixture under argon. The reaction mixture was heated and stirred at 80° C. for 6 hr. After cooling to room temperature, the solvent was evaporated and the residue was quenched with 100 mL water. The mixture was adjusted pH to ˜7 with diluted hydrochloric acid. The mixture was then extracted with EtOAc and the combined organic layer was washed with water and then brine and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with CH2Cl2 to provide the compound 19 (400 mg, 1.55 mmol, 57%) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 8.86 (s, 1H), 7.15 (t, J=8 Hz, 2H), 6.90 (d, J=8 Hz, 1H), 6.78 (m, 5H), 6.57 (t, J=7.2 Hz, 1H), 4.07 (t, J=6.0 Hz, 2H), 3.68 (t, J=6.0 Hz, 2H), 3.45 (q, J=6.8 Hz, 2H), 1.10 (t, J=6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 148.00, 146.35, 145.81, 129.47, 122.24, 120.06, 117.24, 115.04, 112.86, 67.44, 49.79, 45.65, 12.19; HRMS (ESI, positive) m/z calcd. for C16H20NO2 [M+H]+: 258.1494, found: 258.1465; calcd. for C16H19NO2Na [M+Na]+: 280.1313, found: 280.1345. was added to the mixture under argon The reaction mixture was heated After cooling to room temperature the solvent was evaporated the residue was quenched with 100 mL water The mixture was then extracted with EtOAc the combined organic layer was washed with water brine and dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with CH2Cl2

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of compound 3a (500 mg, 2.7 mmol), K2CO3 (750 mg, 5.4 mmol), KI (90 mg, 0.54 mmol) in DMF (50 mL) was bubbled with argon for 10 min Resorcinol (600 mg, 5.4 mmol) was added to the mixture under argon. The reaction mixture was heated and stirred at 80° C. for 6 hr. After cooling to room temperature, the solvent was evaporated and the residue was quenched with 100 mL water. The mixture was adjusted pH to ˜7 with diluted hydrochloric acid. The mixture was then extracted with EtOAc and the combined organic layer was washed with water and then brine and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with CH2Cl2 to provide the compound 18 (380 mg, 1.48 mmol, 55%) as a light-yellow oil. 1H NMR (DMSO-d6, 400 MHz) δ 9.38 (s, 1H), 7.15 (t, J=8 Hz, 2H), 7.04 (t, J=8 Hz, 1H), 6.70 (d, J=8 Hz, 2H), 6.57 (t, J=7.2 Hz, 1H), 6.32 (m, 3H), 4.02 (t, J=5.8 Hz, 2H), 3.64 (t, J=5.8 Hz, 2H), 3.44 (q, J=7 Hz, 2H), 1.10 (t, J=7 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 155.14, 151.95, 142.80, 125.44, 124.66, 111.56, 107.52, 103.46, 102.10, 97.43, 60.60, 44.77, 40.83, 7.34; HRMS (ESI, positive) m/z calcd. for C16H20NO2 [M+H]+: 258.1494, found: 258.1534. was added to the mixture under argon The reaction mixture was heated After cooling to room temperature the solvent was evaporated the residue was quenched with 100 mL water The mixture was then extracted with EtOAc the combined organic layer was washed with water brine and dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with CH2Cl2

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of compound 3a (500 mg, 2.7 mmol), K2CO3 (750 mg, 5.4 mmol), KI (90 mg, 0.54 mmol) in DMF (50 mL) was bubbled with argon for 10 min Resorcinol (600 mg, 5.4 mmol) was added to the mixture under argon. The reaction mixture was heated and stirred at 80° C. for 6 hr. After cooling to room temperature, the solvent was evaporated and the residue was quenched with 100 mL water. The mixture was adjusted pH to ˜7 with diluted hydrochloric acid. The mixture was then extracted with EtOAc and the combined organic layer was washed with water and then brine and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with CH2Cl2 to provide the compound 18 (380 mg, 1.48 mmol, 55%) as a light-yellow oil. 1H NMR (DMSO-d6, 400 MHz) δ 9.38 (s, 1H), 7.15 (t, J=8 Hz, 2H), 7.04 (t, J=8 Hz, 1H), 6.70 (d, J=8 Hz, 2H), 6.57 (t, J=7.2 Hz, 1H), 6.32 (m, 3H), 4.02 (t, J=5.8 Hz, 2H), 3.64 (t, J=5.8 Hz, 2H), 3.44 (q, J=7 Hz, 2H), 1.10 (t, J=7 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 155.14, 151.95, 142.80, 125.44, 124.66, 111.56, 107.52, 103.46, 102.10, 97.43, 60.60, 44.77, 40.83, 7.34; HRMS (ESI, positive) m/z calcd. for C16H20NO2 [M+H]+: 258.1494, found: 258.1534. was added to the mixture under argon The reaction mixture was heated After cooling to room temperature the solvent was evaporated the residue was quenched with 100 mL water The mixture was then extracted with EtOAc the combined organic layer was washed with water brine and dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with CH2Cl2

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

Procedure: 2-(N-ethyl-N-phenylamino)ethanol (10 g, 60 mmol) in CH2Cl2 (150 mL) was reacted with SOCl2 (8.8 mL, 121 mmol). The mixture was heated to reflux for one hour and quenched. The solvent was evaporated and the residue was purified by silica gel column chromatography to provide intermediate 15a (5.54 g, 30 mmol, 50%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.28 (m, 2H), 6.74 (m, 3H), 3.65 (m, 4H), 3.46 (q, J=7.2 Hz, 2H), 1.22 (t, J=7.2 Hz, 3H); HRMS (ESI, positive) m/z calcd. for C10H15ClN [M+H]+: 184.0893, found: 184.0836. The mixture was heated to reflux for one hour quenched The solvent was evaporated the residue was purified by silica gel column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of compound 3a (500 mg, 2.7 mmol), K2CO3 (750 mg, 5.4 mmol), and KI (90 mg, 0.54 mmol) in DMF (50 mL) was bubbled with argon for 10 min Hydroquinone (600 mg, 5.4 mmol) was added to the mixture under argon. The reaction mixture was heated and stirred at 80° C. for 6 hr. The reaction was quenched and the solvent evaporated and purified by silica gel column chromatography to provide compound 3 (400 mg, 1.55 mmol, 57% yield) as a brown oil. 1H NMR (DMSO-d6, 400 MHz) δ 8.92 (s, 1H), 7.14 (m, 2H), 6.75-6.64 (m, 6H), 6.57 (m, 1H), 3.98 (t, J=5.8 Hz, 2H), 3.62 (t, J=5.8 Hz, 2H), 3.41 (q, J=7 Hz, 2H), 1.09 (t, J=7 Hz, 3H). HRMS (ESI, positive) m/z calcd. for C16H20NO2 [M+H]+: 258.1494, found: 258.1436. was added to the mixture under argon The reaction mixture was heated The reaction was quenched the solvent evaporated purified by silica gel column chromatography

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

Procedure: 2-(N-ethyl-N-phenylamino)ethanol (10 g, 60 mmol) in CH2Cl2 (150 mL) was reacted with SOCl2 (8.8 mL, 121 mmol). The mixture was heated to reflux for one hour and quenched. The solvent was evaporated and the residue was purified by silica gel column chromatography to provide intermediate 3a (5.54 g, 30 mmol, 50%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.28 (m, 2H), 6.74 (m, 3H), 3.65 (m, 4H), 3.46 (q, J=7.2 Hz, 2H), 1.22 (t, J=7.2 Hz, 3H); HRMS (ESI, positive) m/z calcd. for C10H15ClN [M+H]+: 184.0893, found: 184.0836. The mixture was heated to reflux for one hour quenched The solvent was evaporated the residue was purified by silica gel column chromatography

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

Procedure: 2-(N-ethyl-N-phenylamino)ethanol (10 g, 60 mmol) in CH2Cl2 (150 mL) was reacted with SOCl2 (8.8 mL, 121 mmol). The mixture was heated to reflux for one hour and quenched. The solvent was evaporated and the residue was purified by silica gel column chromatography to provide intermediate 3a (5.54 g, 30 mmol, 50%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.28 (m, 2H), 6.74 (m, 3H), 3.65 (m, 4H), 3.46 (q, J=7.2 Hz, 2H), 1.22 (t, J=7.2 Hz, 3H); HRMS (ESI, positive) m/z calcd. for C10H15ClN [M+H]+: 184.0893, found: 184.0836. The mixture was heated to reflux for one hour quenched The solvent was evaporated the residue was purified by silica gel column chromatography

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

Procedure: A stirred mixture of 35.6 parts of dimethylaminoethanol in 60 parts of water was heated to 90° and 73.6 parts of N-ethyl-N-(2-chloroethyl)aniline was gradually added. The mixture was heated at 90°-95°. After two and one-half hours there was obtained N,N-dimethyl-N-2-(N'-ethylanilino)ethyl-N-2-hydroxyethylammonium chloride in the form of an aqueous solution. was heated to 90° The mixture was heated at 90°-95°

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 157 parts of N-(3-dimethylaminopropyl)formamide in 20.0 parts of water was heated to 80° C. and over a period of one and one half hours there was added 171 parts of N-ethyl-N-(2-chloroethyl)aniline. The reaction mixture was heated at 95°-100° C. until a small sample when diluted with water gave a clear solution. After about seven hours of heating at 95°-100° C. there was obtained N,N-dimethyl-N-2-(N'-ethylanilino)ethyl-N-3-formamidopropylammonium chloride in the form of an aqueous solution. The reaction mixture was heated at 95°-100° C. until a small sample when gave a clear solution After about seven hours of heating at 95°-100° C.

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

Procedure: A stirred mixture of 35.6 parts of dimethylaminoethanol in 60 parts of water was heated to 90° and 73.6 parts of N-ethyl-N-(2-chloroethyl)aniline was gradually added. The mixture was heated at 90°-95°. After two and one-half hours there are obtained N,N-dimethyl-N-2-(N'-ethylanilino)ethyl-N-2-hydroxyethylammonium chloride in the form of an aqueous solution. was heated to 90° The mixture was heated at 90°-95°