3-ethynylbenzaldehyde

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

Procedure: A multinecked, round bottom flask fitted with a mechanical stirrer, reflux condenser and thermometer, was charged 50.4 g (0.289 mol) of the product of Example XI, 400 ml of distilled water and 1 g of concentrated hydrochloric acid. The mixture was heated to 60° C. and maintained at that temperature for about 4 hours and then cooled to room temperature which yielded the product as a yellow precipitate. The product was filtered, washed with distilled water and allowed to dry on the funnel overnight to yield 33 g (0.254 mol, 87.8% yield). A multinecked, round bottom flask fitted with a mechanical stirrer reflux condenser maintained at that temperature for about 4 hours cooled to room temperature which yielded the product as a yellow precipitate The product was filtered washed with distilled water to dry on the funnel overnight to yield 33 g (0.254 mol, 87.8% yield)

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

Procedure: 5-(trifluoromethyl)pyridin-2-amine (100 mg, 617 μmol, Eq: 1.00), 3-ethynylbenzaldehyde (84.3 mg, 648 μmol, Eq: 1.05) and p-toluenesulfonic acid monohydrate (35.2 mg, 185 μmol, Eq: 0.3) were dissolved in MeOH (1.00 mL) and the intensive yellow solution was stirred for 5 min. To this yellow solution was added dropwise 2-isocyanopropane (42.6 mg, 58.2 μL, 617 μmol, Eq: 1.00) and the corresponding yellow solution was stirred for 2 h. Upon addition of water a yellow precipitate was formed. The solid was filtered off, washed with MeOH/water (1:1) and dried under vacuum to yield the product as a yellow solid (153 mg, 72.2%). MS: 344.0 [M+H]+; 1H-NMR (D6-DMSO): δ 8.90 (s, 1H), 8.36 (s, 1H), 8.25 (d, 1H), 7.71 (d, 1H), 7.50 (t, 1H), 7.46-7.39 (m, 2H), 5.10 (d, 1H), 4.24 (s, 1H), 3.25 (m, 1H), 1.08 (d, 6H). the corresponding yellow solution was stirred for 2 h was formed The solid was filtered off washed with MeOH/water (1:1) dried under vacuum

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

Procedure: 5-(trifluoromethyl)pyridin-2-amine (100 mg, 617 μmol, Eq: 1.00), 3-ethynylbenzaldehyde (84.3 mg, 648 μmol, Eq: 1.05) and p-toluenesulfonic acid monohydrate (35.2 mg, 185 μmol, Eq: 0.3) were dissolved in MeOH (1.00 mL) and the intensive yellow solution was stirred for 5 min. To this yellow solution was added dropwise 2-isocyano-2-methylpropane (51.3 mg, 70.2 μL, 617 μmol, Eq: 1.00) and the corresponding yellow solution was stirred for 2 h. Water was added, the oil was separated from water/MeOH phase and purified by flash column chromatography (40 g SiO2, Hex/EtOAc 100:0 to 0:100) to yield a yellow solid (120 mg, 54.4%). MS: 357.0 [M]+; 1H-NMR (D6-DMSO): δ 8.89 (s, 1H), 8.38 (s, 1H), 8.27 (d, 1H), 7.72 (d, 1H), 7.52-7.40 (m, 3H), 4.94 (s, 1H), 4.22 (s, 1H), 1.04 (s, 9H). the corresponding yellow solution was stirred for 2 h the oil was separated from water/MeOH phase purified by flash column chromatography (40 g SiO2, Hex/EtOAc 100:0 to 0:100)

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

Procedure: 5-(trifluoromethyl)pyridin-2-amine (100 mg, 617 μmol, Eq: 1.00), 3-ethynylbenzaldehyde (84.3 mg, 648 μmol, Eq: 1.05) and p-toluenesulfonic acid monohydrate (35.2 mg, 185 μmol, Eq: 0.3) were dissolved in MeOH (1.00 mL) and the intensive yellow solution was stirred for 5 min. To this yellow solution was added dropwise 2-isocyano-2-methylpropane (51.3 mg, 70.2 μL, 617 μmol, Eq: 1.00) and the corresponding yellow solution was stirred for 2 h. Water was added, the oil was separated from water/MeOH phase and purified by flash column chromatography (40 g SiO2, Hex/EtOAc 100:0 to 0:100) to yield a yellow solid (120 mg, 54.4%). MS: 357.0 [M]+; 1H-NMR (D6-DMSO): δ 8.89 (s, 1H), 8.38 (s, 1H), 8.27 (d, 1H), 7.72 (d, 1H), 7.52-7.40 (m, 3H), 4.94 (s, 1H), 4.22 (s, 1H), 1.04 (s, 9H). the corresponding yellow solution was stirred for 2 h the oil was separated from water/MeOH phase purified by flash column chromatography (40 g SiO2, Hex/EtOAc 100:0 to 0:100)

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

Procedure: In 20 ml of ethyl alcohol was dissolved 1.95 g (15 mmol) of 3-ethynylbenzaldehyde. Thereto were added 1.95 g (15 mmol) of ethyl 3-aminocrotonate and 2.1 g (15 mmol) of allyl acetoacetate, and the admixture was stirred with heating for 16 hours at 80° C. After completing the reaction, the reaction mixture was concentrated to give precipitate. After washing the obtained precipitate with ether, the precipitate was recrystallized from the mixture solution of n-pentane and diethyl ether (n-pentane : diethyl ether=3 : 1 by volume) to give 3.4 g of the desired compound of light yellow needle crystal (yield: 61.5%). the reaction the reaction mixture was concentrated to give precipitate After washing the obtained precipitate with ether the precipitate was recrystallized from the mixture solution of n-pentane and diethyl ether (n-pentane : diethyl ether=3 : 1 by volume)

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

Procedure: To a mixture of 0.65 g (0.005 mol) of 3ethynylbenzaldehyde, 1.08 g (0.0075 mol) of isopropyl acetoacetate and 25 ml of isopropyl alcohol were added 2 to 3 drops of piperidine. After heating the mixture under reflux for 24 hours, 0.65 g (0.005 mol) of ethyl 3-aminocrotonate was added thereto, further the admixture was heated under reflux for 24 hours. After completing the reaction, the reaction mixture was concentrated. The obtained precipitate was purified by subjecting to silica gel column chromatography [eluent: n-hexane to n-hexane: ethyl acetate (7 : 3)] to give 1.1 g of the desired compound (yield: 58.6%). After heating the mixture under reflux for 24 hours further the admixture was heated under reflux for 24 hours the reaction the reaction mixture was concentrated The obtained precipitate was purified

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

Procedure: To a mixture of 0.65 g (0.005 mol) of 3ethynylbenzaldehyde, 1.08 g (0.0075 mol) of isopropyl acetoacetate and 25 ml of isopropyl alcohol were added 2 to 3 drops of piperidine. After heating the mixture under reflux for 24 hours, 0.65 g (0.005 mol) of ethyl 3-aminocrotonate was added thereto, further the admixture was heated under reflux for 24 hours. After completing the reaction, the reaction mixture was concentrated. The obtained precipitate was purified by subjecting to silica gel column chromatography [eluent: n-hexane to n-hexane: ethyl acetate (7 : 3)] to give 1.1 g of the desired compound (yield: 58.6%). After heating the mixture under reflux for 24 hours further the admixture was heated under reflux for 24 hours the reaction the reaction mixture was concentrated The obtained precipitate was purified

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

Procedure: In 30 ml of dry ethyl alcohol was dissolved 1.3 g (10 mmol) of 3-ethynylbenzaldehyde, and 1.43 g (10 mmol) of isopropyl 3-aminocrotonate and 1.6 g (10 mmol) of methoxyethyl acetoacetate were successively added thereto at room temperature. The admixture was reacted under reflux with heating for 12 hours. After completing the reaction, the reaction solution was distilled away under reduced pressure and purified by subjecting to silica gel column chromatography [eluent: n-hexane-chloroform (1 : 1) to chloroform]to give 2.1 g of the chloroform (1 : 1) to chloroform] to give 2.1 g of the desired compound (yield: 53%). were successively added at room temperature The admixture was reacted under reflux with heating for 12 hours the reaction the reaction solution was distilled away under reduced pressure purified to give 2.1 g of the chloroform (1 : 1) to chloroform]