1,1,3-trimethoxypropane

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-cyano-2,6-diaminotoluene (3.56 g), ferric chloride hexahydrate (11.63 g), and zinc chloride (0.499 g) in ethanol (600 mL) is warmed to 65° C. A solution of 1,1,3-trimethoxypropane (5.23 g) in ethanol (90 mL) is added dropwise via syringe pump over a period of 90 minutes. The reaction is then heated to reflux for 2.5 hours. The reaction is cooled to room temperature and the solvent rotary evaporated. The residue is mixed with 300 mL of water and basified to pH=11 with concentrated ammonium hydroxide. The products are extracted with ethyl acetate (4×300 mL), and the combined extracts dried over sodium sulfate and rotary evaporated. The residue is purified by flash chromatography on silica gel, eluting with 50% ethyl acetate/hexane to afford 7-amino-5-cyano-8-methylquinoline as a yellow solid. The reaction is then heated to reflux for 2.5 hours The reaction is cooled to room temperature The products are extracted with ethyl acetate (4×300 mL) the combined extracts dried over sodium sulfate and rotary evaporated The residue is purified by flash chromatography on silica gel eluting with 50% ethyl acetate/hexane

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

Procedure: To a solution of 200 mg (1.66 mmol) of 1,1,3-trimethoxypropane in 25 mL of chloroform was added 5 g (1.66 mmol) of iron (II) chloride on silica (5% by weight) and the slurry was stirred at room temperature for several hours. The slurry was filtered, concentrated in vacuo to about 5 mL and added to a slurry of 200 mg (0.55 mmol) of N2-(4-bromo-2-methoxy-6-methylphenyl)-1-methyl-1H-benzimidazole-2,7-diamine, 1 mL of acetic acid and 2.5 g (5.08 mmol) of MP-CNBH3 in 10 mL of methanol and was stirred overnight. The above aldehyde preparation was repeated each day for 7 days and added to the reaction. The reaction was filtered and concentrated in vacuo to a residue. The residue was purified by flash chromatography eluting with a solution of 40% ethyl acetate/hexanes containing 2% ammonium hydroxide to give 47 mg (18%) of the title compound. The slurry was filtered concentrated in vacuo to about 5 mL was stirred overnight added to the reaction The reaction was filtered concentrated in vacuo to a residue The residue was purified by flash chromatography eluting with a solution of 40% ethyl acetate/hexanes containing 2% ammonium hydroxide

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

Procedure: To a solution of 200 mg (1.66 mmol) of 1,1,3-trimethoxypropane in 25 mL of chloroform was added 5 g (1.66 mmol) of iron (II) chloride on silica (5% by weight) and the slurry was stirred at room temperature for several hours. The slurry was filtered, concentrated in vacuo to about 5 mL and added to a slurry of 200 mg (0.55 mmol) of N2-(4-bromo-2-methoxy-6-methylphenyl)-1-methyl-1H-benzimidazole-2,7-diamine, 1 mL of acetic acid and 2.5 g (5.08 mmol) of MP-CNBH3 in 10 mL of methanol and was stirred overnight. The above aldehyde preparation was repeated each day for 7 days and added to the reaction. The reaction was filtered and concentrated in vacuo to a residue. The residue was purified by flash chromatography eluting with a solution of 40% ethyl acetate/hexanes containing 2% ammonium hydroxide to give 47 mg (18%) of the title compound. The slurry was filtered concentrated in vacuo to about 5 mL was stirred overnight added to the reaction The reaction was filtered concentrated in vacuo to a residue The residue was purified by flash chromatography eluting with a solution of 40% ethyl acetate/hexanes containing 2% ammonium hydroxide

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

Procedure: 51 mg of 4-toluenesulphonic acid are added to a solution of 400 mg of methyl 3-hydroxyl-2-(hydroxymethyl)-2-methylpropanoate and 362 mg of 1,1,3-trimethoxypropane in toluene, and the mixture is stirred at 80° C. for 4 hours. After addition of saturated sodium bicarbonate solution, the organic phase is separated off and dried over sodium sulphate, and the solvent is removed under reduced pressure. The residue is filtered through silica gel (mobile phase cyclohexane/ethyl acetate 4:1). This gives 478 mg of methyl 2-(2-methoxyethyl)-5-methyl-1,3-dioxane-5-carboxylate as a mixture of two isomeric forms in a purity of about 38% (LCMS). the organic phase is separated off dried over sodium sulphate the solvent is removed under reduced pressure The residue is filtered through silica gel (mobile phase cyclohexane/ethyl acetate 4:1) This gives 478 mg of methyl 2-(2-methoxyethyl)-5-methyl-1,3-dioxane-5-carboxylate as a mixture of two isomeric forms in a purity of about 38% (LCMS)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-cyano-2,6-diaminotoluene (3.56 g), ferric chloride hexahydrate (11.63 g), and zinc chloride (0.499 g) in ethanol (600 mL) is warmed to 65° C. A solution of 1,1,3-trimethoxypropane (5.23 g) in ethanol (90 mL) is added dropwise via syringe pump over a period of 90 minutes. The reaction is then heated to reflux for 2.5 hours. The reaction is cooled to room temperature and the solvent rotary evaporated. The residue is mixed with 300 mL of water and basified to pH=11 with concentrated ammonium hydroxide. The products are extracted with ethyl acetate (4×300 mL), and the combined extracts dried over sodium sulfate and rotary evaporated. The residue is purified by flash chromatography on silica gel, eluting with 50% ethyl acetate/hexane to afford 7-amino-5-cyano-8-methylquinoline as a yellow solid. The reaction is then heated to reflux for 2.5 hours The reaction is cooled to room temperature The products are extracted with ethyl acetate (4×300 mL) the combined extracts dried over sodium sulfate and rotary evaporated The residue is purified by flash chromatography on silica gel eluting with 50% ethyl acetate/hexane

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-cyano-2,6-diaminotoluene (3.56 g), ferric chloride hexahydrate (11.63 g), and zinc chloride (0.499 g) in ethanol (600 mL) is heated to 65° C. A solution of 1,1,3-trimethoxypropane (5.23 g) in ethanol (90 mL) is added dropwise via syringe pump over a period of 90 minutes. The reaction is then heated to reflux for 2.5 hours. The reaction is cooled to room temperature and the solvent rotary evaporated. The residue is diluted with 300 mL of water and basified to pH=11 with concentrated ammonium hydroxide. The products are extracted with ethyl acetate (4×300 mL), and the combined extracts dried over sodium sulfate and rotary evaporated. The residue is purified by flash chromatography on silica gel, eluting with 50% ethyl acetate/hexanes to afford 7-amino-5-cyano-8-methylquinoline as a yellow solid. The reaction is then heated to reflux for 2.5 hours The reaction is cooled to room temperature The products are extracted with ethyl acetate (4×300 mL) the combined extracts dried over sodium sulfate and rotary evaporated The residue is purified by flash chromatography on silica gel eluting with 50% ethyl acetate/hexanes

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-cyano-2,6-diaminotoluene (3.56 g), ferric chloride hexahydrate (11.63 g), and zinc chloride (0.499 g) in ethanol (600 mL) is warmed to 65° C. A solution of 1,1,3-trimethoxypropane (5.23 g) in ethanol (90 mL) is added dropwise via syringe pump over a period of 90 minutes. The reaction is then heated to reflux for 2.5 hours. The reaction is cooled to room temperature and the solvent rotary evaporated. The residue is mixed with 300 mL of water and basified to pH=11 with concentrated ammonium hydroxide. The products are extracted with ethyl acetate (4×300 mL), and the combined extracts dried over sodium sulfate and rotary evaporated. The residue is purified by flash chromatography on silica gel, eluting with 50% ethyl acetate/hexane to afford 7-amino-5-cyano-8-methylquinoline as a yellow solid. The reaction is then heated to reflux for 2.5 hours The reaction is cooled to room temperature The products are extracted with ethyl acetate (4×300 mL) the combined extracts dried over sodium sulfate and rotary evaporated The residue is purified by flash chromatography on silica gel eluting with 50% ethyl acetate/hexane