3-hydroxy-4-propan-2-yloxybenzaldehyde

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

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

Procedure: from 3-hydroxy-4-isopropoxybenzaldehyde (prepared in 75% yield by monoalkylation of 3,4-dihydroxybenzaldehyde with isopropyl bromide and K2CO3 in DMF) and 2-bromoethanol there was obtained 3-(2-hydroxy-ethoxy)-4-isopropoxy-benzaldehyde, which was subsequently converted by reaction with 4-aminobenzonitrile and toluene-4-sulphonyl methylisocyanide into methyl (RS)-(4-cyano-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate and then into methyl (RS)-(4-carbainimidoyl-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate hydrochloride (1:1);

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

Procedure: from 3-hydroxy-4-isopropoxybenzaldehyde (prepared in 75% yield by monoalkylation of 3,4-dihydroxybenzaldehyde with isopropyl bromide and K2CO3 in DMF) and 2-bromoethanol there was obtained 3-(2-hydroxy-ethoxy)-4-isopropoxy-benzaldehyde, which was subsequently converted by reaction with 4-aminobenzonitrile and toluene-4-sulphonyl methylisocyanide into methyl (RS)-(4-cyano-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate and then into methyl (RS)-(4-carbainimidoyl-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate hydrochloride (1:1);

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

Procedure: from 3-hydroxy-4-isopropoxybenzaldehyde (prepared in 75% yield by monoalkylation of 3,4-dihydroxybenzaldehyde with isopropyl bromide and K2CO3 in DMF) and 2-bromoethanol there was obtained 3-(2-hydroxy-ethoxy)-4-isopropoxy-benzaldehyde, which was subsequently converted by reaction with 4-aminobenzonitrile and toluene-4-sulphonyl methylisocyanide into methyl (RS)-(4-cyano-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate and then into methyl (RS)-(4-carbamimidoyl-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate hydrochloride (1:1);

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

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

Procedure: The title compound was prepared analogously to intermediate 2 (4-methoxy-3-propoxy-benzaldehyde) by reaction of 3-hydroxy-4-isopropoxy-benzaldehyde ([CAS RN 94283-73-5], F. R. Hewgill, M. C. Pass Australian J. Chem. 1985, 38, 537-554) with 2-bromo-ethanol in DMF using K2CO3 as base. MS (ISP): 224.2 [M+H]+.

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

Procedure: from 3-hydroxy-4-isopropoxybenzaldehyde (prepared in 75% yield by monoalkylation of 3,4-dihydroxybenzaldehyde with isopropyl bromide and K2CO3 in DMF) and 2-bromo-ethanol there was obtained 3-(2-hydroxy-ethoxy)-4-isopropoxy-benzaldehyde, which was subsequently converted by reaction with 4-aminobenzonitrile and toluene-4-sulphonyl methylisocyanide into methyl (RS)-(4-cyano-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate and then into methyl (RS)-(4-carbamimidoyl-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate hydrochloride (1:1);

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

Procedure: from 3-hydroxy-4-isopropoxybenzaldehyde (prepared in 75% yield by monoalkylation of 3,4-dihydroxybenzaldehyde with isopropyl bromide and K2CO3 in DMF) and 2-bromo-ethanol there was obtained 3-(2-hydroxy-ethoxy)-4-isopropoxy-benzaldehyde, which was subsequently converted by reaction with 4-aminobenzonitrile and toluene-4-sulphonyl methylisocyanide into methyl (RS)-(4-cyano-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate and then into methyl (RS)-(4-carbamimidoyl-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate hydrochloride (1:1);

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium carbonate (1.83 g, 13.2 mmol) and benzyl chloride (1.55 mL, 13.5 mmol) were added to a suspension of 3-hydroxy-4-isopropoxybenzaldehyde described in Production Example 171 (1.84 g, 10.2 mmol) in ethanol (20 mL) under nitrogen atmosphere at room temperature, and the mixture was heated and stirred at 90° C. for 2 hours. The mixture was cooled to 0° C. and then 2 M hydrochloric acid, ethyl acetate, and water were added for partition. The organic layer was washed with a saturated saline solution, and the resultant was dried over anhydrous sodium sulfate, and then filtered. The solvent was evaporated, the resultant residue was dissolved in dichloromethane, and the resultant was purified with silica gel column chromatography (n-heptane:ethyl acetate=19:1-3:1). The target fraction was concentrated under vacuum to obtain the title compound (2.59 g, 94%). the mixture was heated The mixture was cooled to 0° C. for partition The organic layer was washed with a saturated saline solution the resultant was dried over anhydrous sodium sulfate filtered The solvent was evaporated the resultant residue was dissolved in dichloromethane the resultant was purified with silica gel column chromatography (n-heptane:ethyl acetate=19:1-3:1) The target fraction was concentrated under vacuum

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available 3,4-dihydroxybenzaldehyde (5 g, 36.2 mmol) and potassium carbonate (5.15 g, 37.3 mmol) were dissolved in N,N-dimethylformamide (20 mL), then 2-bromopropane (3.5 mL, 37.3 mmol) was added under nitrogen atmosphere at room temperature, and the mixture was heated and stirred at 40° C. for 2.5 hours. The reaction mixture was cooled to 0° C., and then 2 M hydrochloric acid, ethyl acetate, and water were added for partition. The aqueous layer was extracted with ethyl acetate, the combined organic layer was washed with water and a saturated saline solution, and the resultant was dried over anhydrous magnesium sulfate and then filtered. The solvent was evaporated, dichloromethane was added to the residue, the precipitate was separated by filtration, and the filtrate was concentrated under vacuum. The residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=19:1-13:7) and then the target fraction was concentrated under vacuum to obtain the title compound (1.84 g, 28%). the mixture was heated The reaction mixture was cooled to 0° C. for partition The aqueous layer was extracted with ethyl acetate the combined organic layer was washed with water a saturated saline solution, and the resultant was dried over anhydrous magnesium sulfate filtered The solvent was evaporated dichloromethane was added to the residue the precipitate was separated by filtration the filtrate was concentrated under vacuum The residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=19:1-13:7) the target fraction was concentrated under vacuum

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

Procedure: from 3-hydroxy-4-isopropoxybenzaldehyde (prepared in 75% yield by monoalkylation of 3,4-dihydroxybenzaldehyde with isopropyl bromide and K2CO3 in DMF) and 2-bromoethanol there was obtained 3-(2-hydroxy-ethoxy)-4-isopropoxy-benzaldehyde, which was subsequently converted by reaction with 4-aminobenzonitrile and toluene-4-sulphonyl methylisocyanide into methyl (RS)-(4-cyano-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate and then into methyl (RS)-(4-carbainimidoyl-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate hydrochloride (1:1);

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

Procedure: from 3-hydroxy-4-isopropoxybenzaldehyde (prepared in 75% yield by monoalkylation of 3,4-dihydroxybenzaldehyde with isopropyl bromide and K2CO3 in DMF) and 2-bromoethanol there was obtained 3-(2-hydroxy-ethoxy)-4-isopropoxy-benzaldehyde, which was subsequently converted by reaction with 4-aminobenzonitrile and toluene-4-sulphonyl methylisocyanide into methyl (RS)-(4-cyano-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate and then into methyl (RS)-(4-carbamimidoyl-phenylamino)-[3-(2-hydroxy-ethoxy)-4-isopropoxy-phenyl]-acetate hydrochloride (1:1);