methyl 3,4-diaminobenzoate

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:0.00; pressure:0.00; stir:

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

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

Procedure: 3,4-Diaminobenzoic acid methyl ester (58.72 mmoles, 9.35 g, 1 equivalent, commercially available from Oakwood Products) was dissolved in acetonitrile (20 ml) and water (200 ml) and cooled to 0-5° C. (ice-water). Cyanogen bromide (8.64 g, 81.55 mmoles, 1.4 equivalent) was added over a period of 5 minutes, and the reaction mixture was allowed to go to room temperature and stirred for 16 hours. The reaction mixture was then evaporated under reduced pressure to 15.60 g of methyl 2-amino-1H-benzo[d]imidazole-5-carboxylate hydrobromide (yield: 98%) which was used directly in the next reaction without any further reaction. 1H-NMR (400 MHz DMSO-d6) δ 12.64 (br s, 2H), 8.80 (bs, 3H), 7.91 (s, 1H), 7.82 (d, 1H), 7.51 (d, 1H), 3.82 (s, 3H). MS (EI): 192 (MH+). to go to room temperature

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3,4-diamino-benzoic acid methyl ester (5.00 g, 30.1 mmol) and THF (40 mL), was added carbonyl diimidazole (7.32 g, 45.1 mmol) at 0° C. The mixture stirred for 16 h, and allowed to warm to 23° C. A solution of 1M aq. HCl (50 mL) was added at 0° C., followed by water (70 mL) and the mixture was stirred for 1 h. The resulting precipitate was filtered and dried under reduced pressure for 18 h to yield the titled compound, which was used in the next step without further purification (5.45 g, 94%). MS (ESI/CI): mass calcd. for C9H8N2O3, 192.1; m/z found, 193.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 11.01 (s, 1H), 10.84 (s, 1H), 7.63 (dd, J=8.2, 1.6 Hz, 1H), 7.47 (s, 1H), 7.02 (d, J=8.2 Hz, 1H), 3.82 (s, 3H). the mixture was stirred for 1 h The resulting precipitate was filtered dried under reduced pressure for 18 h

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

Procedure: 3.0 g of 3,4-diaminobenzoic acid was suspended in methanol, and 1.86 ml of thionyl chloride was then added dropwise. Afterward, thionyl chloride was further added as much as 0.5 ml twice, and the suspension was then heated under reflux for 11 hours. Next, thionyl chloride and methanol were distilled off, and the residue was dissolved in methylene chloride, washed with a 0.5N aqueous sodium hydroxide solution and a saturated sodium chloride solution, and then dried over sodium sulfate. After the solvent was distilled off, the residue was sludged with n-hexane to obtain 3.04 g (93%) of the desired compound. the suspension was then heated under reflux for 11 hours Next, thionyl chloride and methanol were distilled off the residue was dissolved in methylene chloride washed with a 0.5N aqueous sodium hydroxide solution a saturated sodium chloride solution, and then dried over sodium sulfate After the solvent was distilled off

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

Procedure: 2-Ethyl-1-isothiocyanatobenzene (3 mmol) and methyl 3,4-diaminobenzoate (3 mmol) were reacted, following general procedure B, to yield 2-(2-ethylphenylamino)-3H-benzimidazole-5-carboxylic acid methyl ester, which was purified by silica gel chromatography using DCM/ethyl acetate as eluent.

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

Procedure: 2,4-Dichloro-1-isothiocyanatobenzene (5 mmol) and methyl 3,4-diaminobenzoate (5 mmol) were reacted, following general procedure B, to yield 2-(2,4-dichlorophenylamino)-3H-benzimidazole-5-carboxylic acid methyl ester, which was purified by silica gel chromatography using DCM/ethyl acetate as eluent.

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

Procedure: 2-Isothiocyanatopyridine (4 mmol), prepared from 2-aminopyridine employing general procedure A, was reacted with methyl 3,4-diaminobenzoate as described in general procedure B to afford 2-(pyridin-2-ylamino)-1H-benzimidazole-5-carboxylic acid methyl ester. This ester was hydrolyzed, following general procedure C, to obtain 2-(pyridin-2-ylamino)-1H-benzimidazole-5-carboxylic acid.