3-ethoxy-2-methylprop-2-enal

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

Procedure: By the procedure described in Example 2, 5.40 g of 5-amino-4-pyrazolecarbonitrile is reacted with 5.70 g of 3-ethoxy-2-methylacrolein in 25 ml of glacial acid to give the desired product as colorless prisms, mp 193°-194° C.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A sample of 4-trifluoromethylbenzamidine hydrochloride dihydrate (Maybridge, 15.2 g, 58 mmol) was dissolved in 100 mL of methanol and 3-ethoxy-2-methylacrolein (Janssen, 7.8 g, 64 mmol) was added. Sodium methoxide (25% solution in methanol, 14.7 mL) was added and the mixture was heated at 50° C. for 3 h. The cooled reaction mixture was then dded to 500 ml of ice water and stirred for 30 minutes. The white solid was filtered, air dried, dissolved in 300 mL of dichloromethane and dried over magnesium sulfate. The solvent was removed under reduced pressure to yield, after trituration with hexanes, 12.5 g of the product as a white solid melting at 143-146° C. 1H NMR (CDCl3): δ2.37 (s, 3H), 7.73 (d, 2H), 8.53 (d, 2H), 8.66 (s, 2H). The cooled reaction mixture The white solid was filtered air dried dissolved in 300 mL of dichloromethane dried over magnesium sulfate The solvent was removed under reduced pressure to yield

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

Procedure: To a solution of benzamidine hydrochloride (500 mg, 3.19 mmol) and 3-ethoxy-2-methylacrylaldehyde (400 mg, 3.51 mmol) in Methanol (10 mL) was added a NaOMe-solution (30 percent in methanol) dropwise under stirring over 30 minutes. After stirring for 4 hours water (20 mL) was added and mixture was stirred for further 30 minutes at room temperature. After filtration the obtained precipitate was washed with water and dried. White solid. Yield: 220 mg, 41%. 1H NMR (CDCl3, 500 MHz): δH (ppm)=2.34 (s, 3H), 7.44-7.54 (m, 3H), 8.37-8.45 (m, 2H), 8.64 (d, J=0.6 Hz, 2H); 13C NMR (CDCl3, 125 MHz): δC (ppm)=15.7, 128.1, 128.5, 128.8, 130.6, 137.9, 157.6, 162.7; (ESI): m/z=170.97 [M+H]+. was added mixture was stirred for further 30 minutes at room temperature After filtration the obtained precipitate was washed with water dried

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(6-(methylthio)pyrimidin-4-yl)-1H-pyrazole-3,5-diamine (1.0 g, 4.5 mmol) was combined with 3-ethoxy-2-methylacrylaldehyde (0.63 g, 5.3 mmol) in isopropanol (12 mL). Acetic acid (0.1 mL) was added to the reaction mixture which was then sealed in a microwave vessel and heated to 160° C. for 15 min. The reaction mixture was diluted with ethyl acetate (200 mL) and 1N NaOH (60 mL), the layers separated and the organic layer concentrated to 60 mL. This solution was cooled to 0° C. and 77% m-chloroperbenzoic acid (1.9 g, 8.5 mmol) was added. After 1 hr. a yellow precipitate formed which was filter off, washed with ethyl acetate and dried to give the product, 0.39 g, 30% yield. LCMS MH+289.29. H NMR (500 MHz, DMSO-d6) 9.02 (s, 1H) 8.91 (s, 1H), 8.88 (s, 1H), 8.54 (s, 1H), 7.14 (s, 2H), 2.91 (s, 3H), 2.34 (s, 3H). was then sealed in a microwave vessel the layers separated the organic layer concentrated to 60 mL This solution was cooled to 0° C. a yellow precipitate formed which was filter off washed with ethyl acetate dried to give the product, 0.39 g, 30% yield

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

Procedure: A mixture of 3-ethoxy-2-methyl-2-propenal, (E)- and (Z)- (4.0 g, 35 mmol), 1,1-dimethylhydrazine (2.73 g, 46 mmol) and acetic acid (0.04 g, 0.7 mmol) in diethyl ether is refluxed for one hour, cooled, washed sequentially with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to give the title product as a yellow oil. cooled washed sequentially with water and brine dried over anhydrous magnesium sulfate concentrated in vacuo

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

Procedure: A mixture of 3-ethoxy-2-methyl-2-propenal, (E)- and (Z)- (4.0 g, 35 mmol), 1,1-dimethylhydrazine (2.73 g, 46 mmol) and acetic acid (0.04 g, 0.7 mmol) in diethyl ether is refluxed for one hour, cooled, washed sequentially with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to give the title product as a yellow oil. cooled washed sequentially with water and brine dried over anhydrous magnesium sulfate concentrated in vacuo

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

Procedure: By the procedure described in Example 2, 5.40 g of 5-amino-4-pyrazolecarbonitrile is reacted with 5.70 g of 3-ethoxy-2-methylacrolein in 25 ml of glacial acid to give the desired product as colorless prisms, mp 193°-194° C.

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

Procedure: By the procedure described in Example 2, 5.40 g of 5-amino-4-pyrazolecarbonitrile is reacted with 5.70 g of 3-ethoxy-2-methylacrolein in 25 ml of glacial acid to give the desired product as colorless prisms, mp 193°-194° C.

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

Procedure: 2-Hydroxymethyl-5-methylpyrimidine was prepared by the reaction of 3-ethoxy-2-methyl acrolein and hydroxyacetamidine hydrochloride following a similar procedure to that described by Kim and McKee (J. Org. Chem., 35, 455 (1970)). Proton magnetic resonance spectrum (CDCl3 ; δ in ppm): 2.32 (3H,s); 3.6 (1H,bs); 4.80 (2H,s); 8.54 (2H,s).

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

Procedure: A mixture of 3-amino-5,5-dimethylcyclohex-2-enone (27.8g., 0.2 mol.) and 2-methyl-3-ethoxyacrolein (22.8 g., 0.2 mol.), in an apparatus equipped for downward distillation, was heated in an oil bath at 120° until the theoretical quantity of distillate was collected (13 ml.) The cooled residue was diluted with 2N HCl (50 ml.), extracted with ethyl acetate (3 × 50 ml.) and the combined extracts discarded. The aqueous solution was adjusted to pH 9.0 with sodium carbonate and extracted with ethyl acetate (3 × 50 ml.). The combined extracts were dried (MgSO4) and the solvent removed in vacuo and the residual oil distilled to give the title compound as a colourless oil (23 g., 53%) b.p. 83°/0.2 mm Hg. (RT = 2 min., 2% OV17, T=150° C). in an apparatus equipped for downward distillation was heated in an oil bath at 120° until the theoretical quantity of distillate was collected (13 ml.) The cooled residue was diluted with 2N HCl (50 ml.) extracted with ethyl acetate (3 × 50 ml.) extracted with ethyl acetate (3 × 50 ml.) The combined extracts were dried (MgSO4) the solvent removed in vacuo the residual oil distilled

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

Procedure: A mixture of 3-aminocyclohex-2-enone (11.1 g. 0.1m) and 3-amino-2-methylacrolein (8.5 g. 0.1 m) in toluene (15 ml.) was heated at reflux below a Dean and Stark water separator for 48 hours. The solvent was removed and the residual oil distilled at 0.2 mm Hg to give the title compound as a colourless crystalline solid (0.5 g, 4%). was heated The solvent was removed the residual oil distilled at 0.2 mm Hg

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

Procedure: A mixture of cyclohexane-1,3-dione (11.2 g. 0.1 m), 3-amino-2-methylacrolein (8.5 g. 0.1m) triethylamine (5 ml.) and ammonium acetate (100 mg) were heated with stirring at 120° in an oil bath for 12 hours. The cooled reaction mixture was diluted with ether (50 ml.) and the solution washed with 2N HCl (3 × 15 ml.) The combined washings were adjusted to pH 9.0 with sodium carbonate and extracted with ether (3 × 50 ml.) The combined extracts were dried, evaporated in vacuo and the residual oil distilled at 0.2 mm Hg to give the title compound as a colourless crystalline solid b.p. 80° (7.5 g. 48%). were heated The cooled reaction mixture the solution washed with 2N HCl (3 × 15 ml.) The combined washings extracted with ether (3 × 50 ml.) The combined extracts were dried evaporated in vacuo the residual oil distilled at 0.2 mm Hg