methyl 3-amino-4-formylbenzoate

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

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

Procedure: To a solution of 25 mL of ethanol/glacial acetic acid/water (2:2:1) were added 0.6 g (2.9 mmol) of methyl 4-formyl-3-nitrobenzoate, 1.2 g (21.4 mmol) of iron powder and 0.01 mL of concentrated hydrochloric acid and the mixture was refluxed with stirring for 15 minutes. Then the iron was separated off, the solution was diluted with water and extracted with methylene chloride. The combined organic extracts were washed with water, dried, and evaporated down. Yield: 0.3 g (58% of theory); Rf value: 0.74 (silica gel, methylene chloride/methanol=9.5:0.5). the mixture was refluxed Then the iron was separated off the solution was diluted with water extracted with methylene chloride The combined organic extracts were washed with water dried evaporated down

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

Procedure: To a solution of 25 mL of ethanol/glacial acetic acid/water (2:2:1) were added 0.6 g (2.9 mmol) of methyl 4-formyl-3-nitrobenzoate, 1.2 g (21.4 mmol) of iron powder and 0.01 mL of concentrated hydrochloric acid and the mixture was refluxed with stirring for 15 minutes. Then the iron was separated off, the solution was diluted with water and extracted with methylene chloride. The combined organic extracts were washed with water, dried, and evaporated down. Yield: 0.3 g (58% of theory); Rf value: 0.74 (silica gel, methylene chloride/methanol=9.5:0.5). the mixture was refluxed Then the iron was separated off the solution was diluted with water extracted with methylene chloride The combined organic extracts were washed with water dried evaporated down

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

Procedure: Dissolve 3-amino-4-hydroxymethyl-benzoic acid methyl ester (step (c), 4.2 g, 23.3 mmol) in 125 mL of anhydrous CH2Cl2 and add MnO2 (20.2 g, 232.8 mmol) and stirred at RT. After 5 h, the solution was filtered through Celite and concentrated to afford the title compound as a yellow solid upon drying under vacuum. MS m/z: 180.1 (M+1). the solution was filtered through Celite concentrated

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

Procedure: To a solution of 25 ml of ethanol/glacial acetic acid/water (2:2:1) were added 0.6 g (2.9 mmol) of methyl 4-formyl-3-nitro-benzoate, 1.2 g (21.4 mmol) of iron powder and 0.01 ml of concentrated hydrochloric acid and the mixture was refluxed with stirring for 15 minutes. Then the iron was separated off, the solution was diluted with water and extracted with methylene chloride. The combined organic extracts were washed with water, dried and evaporated down. Yield: 0.3 g (58% of theory), Rf value: 0.74 (silica gel, methylene chloride/methanol=9.5:0.5) the mixture was refluxed Then the iron was separated off the solution was diluted with water extracted with methylene chloride The combined organic extracts were washed with water dried evaporated down

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

Procedure: To a mixture of methyl 3-amino-4-formylbenzoate (110 mg, 0.614 mmol) in 6 mL THF plus 4 mL saturated NaHCO3 and 1 mL H2O at rt was added ethyl chloroformate (0.070 mL, 0.737 mmol) at the reaction stirred at rt. After 50 min, an additional 0.5 mL saturated NaHCO3 and 5 drops ethyl chloroformate was added. At 17.5 hours the mixture was heated to 60° C., 1 mL saturated Na2CO3 added, and 5 drops ethyl chloroformate added. Then to push reaction to completion, a small scoop of solid Na2CO3 was added and additional ethyl chloroformate added drop-wise until the reaction was approximately 80% complete (45 hours total reaction time). The reaction was partitioned between EtOAc and aqueous NaHCO3 solution, the EtOAc layer washed with brine, dried with Na2SO4, and evaporated. The solid was crystallized from hexane/EtOAc and the filtrate chromatographed eluting with 2.5% MeOH/CHCl3. The impure products from crystallization and chromatography were combined and then recrystallized from hexane/EtOAc to give the title compound as a light yellow solid (63.8 mg, 41%). 1H NMR (CDCl3) δ: 10.53 (br. s, 1H), 10.00 (d, J=0.6 Hz, 1H), 9.11-9.12 (m, 1H), 7.80-7.84 (m, 1H), 7.72-7.76 (m, 1H), 4.28 (q, J=7.2 Hz, 2H), 3.95 (s, 3H), 1.35 (t, J=7.2 Hz, 3H). At 17.5 hours the mixture was heated to 60° C. reaction to completion approximately 80% complete (45 hours total reaction time) The reaction was partitioned between EtOAc and aqueous NaHCO3 solution the EtOAc layer washed with brine dried with Na2SO4 evaporated The solid was crystallized from hexane/EtOAc the filtrate chromatographed eluting with 2.5% MeOH/CHCl3 The impure products from crystallization and chromatography recrystallized from hexane/EtOAc

Conditions: temp:145.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl 4-formyl-3-aminobenzoate (1 eq) was added urea (5 eq) and the mixture was heated to 145° C. for 16 h. To the crude was added water and the precipitated solid was filtered to give methyl 2-hydroxyquinazolin-7-carboxylate in quantitative yield. ES/MS m/z 205 (MH+). the precipitated solid was filtered

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

Procedure: To a 1:1 mixture of ethanol and acetic acid was added methyl4-formyl-3-nitrobenzoate (1 eq) and Fe dust (3 eq) was added in portions. The reduction was complete in 1 h. The reaction mixture was filtered and then concentrated and partitioned between ethyl acetate and water. The organic layer was washed with saturated sodium bicarbonate and dried and concentrated to give methyl 4-formyl-3-aminobenzoate in 85% yield. ES/MS m/z 180 (MH+). was added in portions The reaction mixture was filtered concentrated partitioned between ethyl acetate and water The organic layer was washed with saturated sodium bicarbonate dried concentrated

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

Procedure: Following the same reaction procedure and workup as for Compound 405f (235 mg, 1.31 mmol) of Compound 53 was reacted with the product of the previous reaction, Compound 424b (360 mg, 1.31 mmol), in ethanol (12 mL) using 10% w/v KOH in ethanol (1.1 mL) to produce the title compound (210 mg, 40% yield).

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

Procedure: Following the same reaction procedure and workup for Compound 405f, 500 mg (2.8 mmol) of Compound 53 was reacted with 340 mg (2.8 mmol) phenylacetaldehyde to produce 603 mg (87% yield) of the title intermediate.

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

Procedure: To a solution of 25 mL of ethanol/glacial acetic acid/water (2:2:1) were added 0.6 g (2.9 mmol) of methyl 4-formyl-3-nitrobenzoate, 1.2 g (21.4 mmol) of iron powder and 0.01 mL of concentrated hydrochloric acid and the mixture was refluxed with stirring for 15 minutes. Then the iron was separated off, the solution was diluted with water and extracted with methylene chloride. The combined organic extracts were washed with water, dried, and evaporated down. Yield: 0.3 g (58% of theory); Rf value: 0.74 (silica gel, methylene chloride/methanol=9.5:0.5). the mixture was refluxed Then the iron was separated off the solution was diluted with water extracted with methylene chloride The combined organic extracts were washed with water dried evaporated down