2-Propenal, 3-amino-, (2E)-

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-amino acrolein (4.52 g) and acetylacetone (7.64 g) was added catalytic amount of ammonium acetate. The mixture was heated for 19 hours at ca. 110° C., After cooling to room temperature, the mixture was poured into 100 ml of isopropyl ether and dried over magnesium sulfate. The resultant mixture was filtered off by suction in vacuo to remove an insoluble material and the filtrate was concentrated in vacuo. The crude compound was purified by column chromatography on silica gel with chloroform to give 3-acetyl-2-methylpyridine (3.58 g) as a yellow oil. After cooling to room temperature dried over magnesium sulfate The resultant mixture was filtered off by suction in vacuo to remove an insoluble material the filtrate was concentrated in vacuo The crude compound was purified by column chromatography on silica gel with chloroform

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-amino acrolein (4.52 g) and acetylacetone (7.64 g) was added catalytic amount of ammonium acetate. The mixture was heated for 19 hours at ca. 110° C., After cooling to room temperature, the mixture was poured into 100 ml of isopropyl ether and dried over magnesium sulfate. The resultant mixture was filtered off by suction in vacuo to remove an insoluble material and the filtrate was concentrated in vacuo. The crude compound was purified by column chromatography on silica gel with chloroform to give 3-acetyl-2-methylpyridine (3.58 g) as a yellow oil. After cooling to room temperature dried over magnesium sulfate The resultant mixture was filtered off by suction in vacuo to remove an insoluble material the filtrate was concentrated in vacuo The crude compound was purified by column chromatography on silica gel with chloroform

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-oxo-1,4,5,6,7,8-hexahydrocyclohepta(b)pyrrole-3-carboxylic acid ethyl ester (7.0 g, 31.67 mmol), 3-amino-prop-2-enal (3.37 g, 47.5 mmol) and ammonium acetate (365 mg, 4.75 mmol) in triethylamine (7 mL) is heated at 110° C. for 4 h. It is cooled to room temperature and the solid residue is dissolved in 100 mL dichloromethane and 100 mL sat. NaHCO3 solution. Layers are separated and the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL). Combined organic layers are dried (Na2SO4) and evaporated. Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1), provides 3,4,5,6-tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid ethyl ester (1.6 g, 20%) as off-white solid. 1H NMR (400 MHz, CD3OD) δ 1.247 (3H, t), 2.227 (2H, m), 2.631 (4H, m), 4.197 (2H, q), 7.170 (1H, m), 7.405 (1H, s), 7.686 (1H, d), 8.375 (1H, d). MS (ES+) 257 (M+1). It is cooled to room temperature Layers are separated the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL) Combined organic layers are dried (Na2SO4) evaporated Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-oxo-1,4,5,6,7,8-hexahydro-cyclohepta(b)pyrrole-3-carboxylic acid ethyl ester (7.0 g, 31.67 mmol), 3-amino-prop-2-enal (3.37 g, 47.5 mmol) and ammonium acetate (365 mg, 4.75 mmol) in triethylamine (7 mL) is heated at 110° C. for 4 h. It is cooled to room temperature and the solid residue is dissolved in 100 mL dichloromethane and 100 mL sat. NaHCO3 solution. Layers are separated and the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL). Combined organic layers are dried (Na2SO4) and evaporated. Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1), provides 3,4,5,6-tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid ethyl ester (1.6 g, 20%) as off-white solid. 1H NMR (400 MHz, CD3OD) δ1.247 (3H, t), 2.227 (2H, m), 2.631 (4H, m), 4.197 (2H, q), 7.170 (1H, m), 7.405 (1H, s), 7.686 (1H, d), 8.375 (1H, d). MS (ES+) 257 (M+1) It is cooled to room temperature Layers are separated the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL) Combined organic layers are dried (Na2SO4) evaporated Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-oxo-1,4,5,6,7,8-hexahydro-cyclohepta(b)pyrrole-3-carboxylic acid ethyl ester (7.0 g, 31.67 mmol), 3-amino-prop-2-enal (3.37 g, 47.5 mmol) and ammonium acetate (365 mg, 4.75 mmol) in triethylamine (7 mL) is heated at 110° C. for 4 h. It is cooled to room temperature and the solid residue is dissolved in 100 mL dichloromethane and 100 mL sat. NaHCO3 solution. Layers are separated and the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL). Combined organic layers are dried (Na2SO4) and evaporated. Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1), provides 3,4,5,6-tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid ethyl ester (1.6 g, 20%) as off-white solid. 1H NMR (400 MHz, CD3OD) δ1.247 (3H, t), 2.227 (2H, m), 2.631 (4H, m), 4.197 (2H, q), 7.170 (1H, m), 7.405 (1H, s), 7.686 (1H, d), 8.375 (1H, d). MS (ES+) 257 (M+1) It is cooled to room temperature Layers are separated the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL) Combined organic layers are dried (Na2SO4) evaporated Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1)

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

Procedure: 3-Methoxyacrolein was prepared from 1,1,3,3-tetramethoxypropane (Helv. Chim. Acta 1959, 42, 851) and converted to 3-aminoacrolein according to the method of Brietmaier and Gasenmann (Chem. Ber. 1971, 104, 665-7). 5,6,7,8-Tetrahydroquinoline was prepared from 3-aminoacrolein as described by Brietmaier and Bayer (Tet. Letts 1970, 38, 3291). A mixture of 3-aminoacrolein (7.3 gm, 0.1 m) and cyclohexanone (12 gm., 0.12m) was treated with triethylamine (5 ml.) and piperidinium acetate (0.1 gr) and the mixture heated in an oil bath at 120° for 24 hours. The cooled reaction mixture was dissolved in ether (100 ml.), washed with water and 2N HCl (2 × 20 ml.) and the acid washings combined, made basic with sodium carbonate and extracted with ether. The combined extracts were dried, evaporated and the residue distilled to give the title compound as a pale yellow oil (4.5 gm, 35%) b.p. 100°/15 mm. the mixture heated in an oil bath at 120° for 24 hours The cooled reaction mixture washed with water and 2N HCl (2 × 20 ml.) extracted with ether The combined extracts were dried evaporated the residue distilled

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-benzyloxycarbonylaminocyclohexanone (13.75 g, 55.6 mmol), 3-aminopropenal (5.57 g, 78.4 mmol), and ammonium acetate (0.14 g, 1.78 mmol) in triethylamine (85 mL) was stirred at 115° C. under nitrogen for 3 d. The reaction mixture was then partitioned between chloroform and water. The organic layer was separated, washed sequentially with water, saturated aqueous ammonium chloride solution and brine, dried over anhydrous magnesium sulfate, and evaporated under vacuum to yield a residue. The residue was subjected to silica gel chromatography (eluted with 5% methanol in methylene chloride) to obtain the title compound (1.67 g, 10.5%) as a brown oil. 3C NMR (400 MHz, CDCl3) δ 155.6, 147.5, 137.2, 136.4, 129.2, 128.5, 128.1, 121.2, 66.7, 46.2, 35.2, 30.1, 28.7. 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J=4.4 Hz, 1H), 7.27 (m, 6H), 6.98 (dd, J=4.8, 7.5 Hz, 1H), 5.03 (s, 2H), 4.85 (br s, 1H), 4.00 (br s, 1H), 3.06 (d, J=16.3 Hz, 1H), 2.97 (t, J=6.6 Hz, 2H), 2.62 (dd, J=7.9, 16.0 Hz, 1H), 2.08 (d, J=8.4 Hz, 1H), 1.82 (m, 1H). The reaction mixture was then partitioned between chloroform and water The organic layer was separated washed sequentially with water, saturated aqueous ammonium chloride solution and brine dried over anhydrous magnesium sulfate evaporated under vacuum to yield a residue The residue was subjected to silica gel chromatography (eluted with 5% methanol in methylene chloride)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-amino acrolein (4.52 g) and acetylacetone (7.64 g) was added catalytic amount of ammonium acetate. The mixture was heated for 19 hours at ca. 110° C., After cooling to room temperature, the mixture was poured into 100 ml of isopropyl ether and dried over magnesium sulfate. The resultant mixture was filtered off by suction in vacuo to remove an insoluble material and the filtrate was concentrated in vacuo. The crude compound was purified by column chromatography on silica gel with chloroform to give 3-acetyl-2-methylpyridine (3.58 g) as a yellow oil. After cooling to room temperature dried over magnesium sulfate The resultant mixture was filtered off by suction in vacuo to remove an insoluble material the filtrate was concentrated in vacuo The crude compound was purified by column chromatography on silica gel with chloroform

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-oxo-1,4,5,6,7,8-hexahydrocyclohepta(b)pyrrole-3-carboxylic acid ethyl ester (7.0 g, 31.67 mmol), 3-amino-prop-2-enal (3.37 g, 47.5 mmol) and ammonium acetate (365 mg, 4.75 mmol) in triethylamine (7 mL) is heated at 110° C. for 4 h. It is cooled to room temperature and the solid residue is dissolved in 100 mL dichloromethane and 100 mL sat. NaHCO3 solution. Layers are separated and the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL). Combined organic layers are dried (Na2SO4) and evaporated. Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1), provides 3,4,5,6-tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid ethyl ester (1.6 g, 20%) as off-white solid. 1H NMR (400 MHz, CD3OD) δ 1.247 (3H, t), 2.227 (2H, m), 2.631 (4H, m), 4.197 (2H, q), 7.170 (1H, m), 7.405 (1H, s), 7.686 (1H, d), 8.375 (1H, d). MS (ES+) 257 (M+1). It is cooled to room temperature Layers are separated the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL) Combined organic layers are dried (Na2SO4) evaporated Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-oxo-1,4,5,6,7,8-hexahydro-cyclohepta(b)pyrrole-3-carboxylic acid ethyl ester (7.0 g, 31.67 mmol), 3-amino-prop-2-enal (3.37 g, 47.5 mmol) and ammonium acetate (365 mg, 4.75 mmol) in triethylamine (7 mL) is heated at 110° C. for 4 h. It is cooled to room temperature and the solid residue is dissolved in 100 mL dichloromethane and 100 mL sat. NaHCO3 solution. Layers are separated and the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL). Combined organic layers are dried (Na2SO4) and evaporated. Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1), provides 3,4,5,6-tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid ethyl ester (1.6 g, 20%) as off-white solid. 1H NMR (400 MHz, CD3OD) δ1.247 (3H, t), 2.227 (2H, m), 2.631 (4H, m), 4.197 (2H, q), 7.170 (1H, m), 7.405 (1H, s), 7.686 (1H, d), 8.375 (1H, d). MS (ES+) 257 (M+1) It is cooled to room temperature Layers are separated the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL) Combined organic layers are dried (Na2SO4) evaporated Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1)

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

Procedure: 3-Methoxyacrolein was prepared from 1,1,3,3-tetramethoxypropane (Helv. Chim. Acta 1959, 42, 851) and converted to 3-aminoacrolein according to the method of Brietmaier and Gasenmann (Chem. Ber. 1971, 104, 665-7). 5,6,7,8-Tetrahydroquinoline was prepared from 3-aminoacrolein as described by Brietmaier and Bayer (Tet. Letts 1970, 38, 3291). A mixture of 3-aminoacrolein (7.3 gm, 0.1 m) and cyclohexanone (12 gm., 0.12m) was treated with triethylamine (5 ml.) and piperidinium acetate (0.1 gr) and the mixture heated in an oil bath at 120° for 24 hours. The cooled reaction mixture was dissolved in ether (100 ml.), washed with water and 2N HCl (2 × 20 ml.) and the acid washings combined, made basic with sodium carbonate and extracted with ether. The combined extracts were dried, evaporated and the residue distilled to give the title compound as a pale yellow oil (4.5 gm, 35%) b.p. 100°/15 mm. the mixture heated in an oil bath at 120° for 24 hours The cooled reaction mixture washed with water and 2N HCl (2 × 20 ml.) extracted with ether The combined extracts were dried evaporated the residue distilled