3-(DIMETHYLAMINO)ACROLEIN

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

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

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

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

Conditions: temp:-23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1.1 mL (11.9 mmol) of phosphorus oxychloride in 15 mL of acetonitrile was allowed to react with 1.2 mL (11.9 mmol) of 3-dimethylaminoacrolein at -23° C. After 0.25 hour at -23° C., 1.4 g (7.9 mmol) of 2-methyl-4-(4'-fluorophenyl)furan in 10 mL of acetonitrile was added dropwise. The reaction mixture was stirred at -23° C. for 0.15 hour then at 24° C. for 2 hours. The reaction was quenched upon treatment with 20 mL of 1M NaOH and extracted three times with CHCl3. The CHCl3 layers were combined, dried (MgSO4) and concentrated under reduced pressure. Column chromatography (3:1 hexanes-diethyl ether) of the residue on silica gel produced 1.76 g (97%) of 3-(5-methyl-3-p-fluorophenyl-furan-2-yl)acrylaldehyde as a solid (m.p. 89°-90° C.), homogeneous by TLC and spectroscopic criteria; Rf 0.58 (1:1 hexanes-diethyl ether); IR (KBr) 1655, 1600, 1205, 1118, 1095 cm-1 ; 1HNMR (300 MHz, CDCl3) 9.60 (d, 1H, J=10.5 Hz), 7.41 (m, 2H), 7.27 (d, 1H, J=15 Hz), 7.18 (t, 2H, J=9.0 Hz), 6.64 (dd, 1H, J=10.5 Hz, 15 Hz), 6.32 (s, 1H), 2.42 (s, 3H). at 24° C. for 2 hours The reaction was quenched upon treatment with 20 mL of 1M NaOH extracted three times with CHCl3 dried (MgSO4) concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Pyridinium tetrafluoroborate (2.21 g, 13.3 mmol) was added to a solution of (3E)-4-(dimethylamino)-3-buten-2-one (1.54 ml, 13.3 mmol) in 13.5 ml acetic anhydride/acetic acid (2:1). The resulting suspension was cooled to 0° C. and 3-dimethylaminoacroleine (1.33 ml, 13.3 mmol) was added over a period of 1 h under vigorous stirring and cooling with an ice bath receiving a red-brown precipitate. The cool reaction mixture was filtered and the remaining solid was washed with diethylether several times and dried under reduced pressure. The pentamethinium salt was obtained as orange crude product (2.69 g, 96%) and was used without any further purification. cooling with an ice bath The cool reaction mixture was filtered the remaining solid was washed with diethylether several times dried under reduced pressure

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

Procedure: A solution of 3-dimethylaminoacrylaldehyde (3.68 g) in dry acetonitrile (10 ml) was slowly added over a 30-minute period to a solution of phosphorus oxychloride (6.07 g) in dry acetonitrile (10 ml) with stirring at 0°-10° C. under nitrogen. A solution of 5,6-dihydro-4,4-dimethyl-1-(4-fluorophenyl)-4H-pyrrolo[3,2,1-ij]quinoline (3.70 g) in dry acetonitrile (9 ml) was slowly added to the reaction mixture at the same temperature. The reaction mixture was refluxed for 7 l hours under nitrogen, cooled to room temperature and slowly poured into a cold solution of sodium hydroxide (6.34 g) in water (130 ml) with stirring. The reaction mixture was extracted twice with toluene. The extracts were combined, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was chromatographed on a silica gel column eluting with a mixture of n-hexane and ethyl acetate (5:1, V/V). The fractions containing the object compound were collected and evaporated under reduced pressure. The residual oil was triturated with n-hexane to give yellow crystals of (E)-3-[5,6-dihydro-4,4-dimethyl-1-(4-fluorophenyl)-4H-pyrrolo[3,2,1-ij]quinolin-2-yl]acrylaldehyde (3.11 g). The reaction mixture was refluxed for 7 l hours under nitrogen with stirring The reaction mixture was extracted twice with toluene washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate evaporated under reduced pressure The residue was chromatographed on a silica gel column eluting with a mixture of n-hexane and ethyl acetate (5:1, V/V) The fractions containing the object compound were collected evaporated under reduced pressure The residual oil was triturated with n-hexane

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of phosphorus oxychloride (1.69 ml, 18.15 mmoles) in 50 ml of acetonitrile cooled in an ice bath was added 3-dimethylaminoacrolein (1.68 ml, 16.75 mmoles) dropwise over 3 minutes. The mixture was stirred for 5 minutes and a solution of 7.9-di-(4-fluorophenyl)-spiro[4.5]-deca-6,8-diene (4.5 g, 13.96 mmoles) in 150 ml of warm acetonitrile was added dropwise over 30 minutes. The mixture was stirred at room temperature for 16 hours and was then heated in an oil bath at 60° C. for 6 hours. The mixture was cooled and poured into 400 ml of cold 1N sodium hydroxide. The mixture was extracted with ether. The ether was washed with water and evaporated in vacuo. The mixture was stirred at room temperature for 16 hours The mixture was cooled The mixture was extracted with ether The ether was washed with water evaporated in vacuo

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: 16.2 g (0.09 mol) of 1-(2-acetylaminoethyl)-2,5-dimethylpyrrole and 10 g (0.1 mol) of 3-dimethylaminoacrolein are dissolved in 80 ml of 1,2-dichloroethane. 9 ml (0.098 mol) of phosphorus oxychloride are added dropwise at -10° C. After 20 minutes, 41 g (0.5 mol) of sodium acetate in 150 ml of water are added, the mixture is stirred at room temperature for 18 hours and heated at 70° C. for 2 hours, the phases are separated, the organic phase is chromatographed over a silica gel column and the product is recrystallized from isopropanol. heated at 70° C. for 2 hours the phases are separated the organic phase is chromatographed over a silica gel column the product is recrystallized from isopropanol

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Pyridine-2,6-diamine (0.30 g, 2.8 mmol), 3-dimethylaminoacrolein (90%, 0.30 g, 2.8 mmol), and polyphosphoric acid (PPA) (2.7 mL) were combined and the reaction mixture was heated to 120° C. for 10 hours. Then, the reaction mixture was poured on ice water and neutralized with solid sodium carbonate. The resulting aqueous mixture was extracted three times with ethyl acetate and the combined organic extracts were washed with brine, concentrated, and purified by column chromatography (EtOAc/hexanes) to give [1,8]-naphthyridin-2-ylamine Yield 85 mg (21%). LCMS (ESI): calc. C8H7N3=145; obs. M+H=146. The resulting aqueous mixture was extracted three times with ethyl acetate the combined organic extracts were washed with brine concentrated purified by column chromatography (EtOAc/hexanes)