Benzoic acid, 3,4-diamino-2-methoxy-, methyl ester (9CI)

Compound 63D (2.5 g, 9.6 mmol), 16mL of triethylamine and palladium on carbon (2.3g) in methanol, nitrogen protection, Stir for 16 hours at 4 atmospheres, after the reaction is over, Palladium carbon was removed by filtration, and the filtrate was spun dry and separated by column chromatography (petroleum ether / ethyl acetate =3:2) Compound 63E (1.3 g, 40% yield) was obtained.(c) 3, 4-Diamino-2-methoxy-3-nitrobenzoic acid methyl ester; Pd-C (10 wt%, 4.5 g) is added in one portion to a stirred solution of the amine (5 g) in methanol (250 cm3) at room temperature. Then, triethylamine (30 cm3) is added and the resulting mixture is transferred to a parr apparatus. After stirring for 8 hours, the reaction mixture is filtered through Celiez filter material and washed with methanol (100 cm3). Evaporation under reduced pressure gives the crude product containing residual triethylamine. Purification by column chromatography on silica with iso-hexane-EtOAc (1: 4) as eluent gives the diamine as a brown solid.3, 4-Diamino-2-methoxy-benzoic Acid Methyl Ester (13). Amine 12 (4.8 g, 18.4 mmol) was dissolved in methanol (250 mL) and the resulting solution was intensively degassed for 10 min with Ar. Pd/C (10 wt %, 4.5 g) was added, followed by Et3N (30 mL) and the resulting mixture was transferred to a parr apparatus. After being stirred for 6 h under a hydrogen atmosphere at 5 atm, the reaction mixture was filtered through a pad of Celite and rinsed with methanol. Evaporation of the solvent yielded crude diamine 13 as a brown gum (with residual Et3N). Data for 13: Rf0.43 (hexane/EtOAc 1:4). 1H NMR (300 MHz, DMSOd6): delta 3.62 (s, 3H), 3.67 (s, 3H), 4.38 (brs, 2H), 5.38 (brs, 2H), 6.30 (d, J=8.2 Hz, 1H), 6.96 (d, J=8.2 Hz, 1H). 13C NMR (75 MHz, DMSO-d6): delta 51.77, 60.53, 109.36, 111.27, 121.35, 127.78, 141.95, 147.61. MS (ESI): m/z (rel intensity) 197 (55).Compound 63E (1.3 g, 6.6 mmol)And 3, 5-dichlorosalicylaldehyde (1.52 g, 7.95 mmol)Stirring in 25 mL of nitrobenzene for two hours, after cooling to room temperature, A large amount of precipitated precipitated, filtered, and the filter cake was washed with petroleum ether.Compound 63F (2.0 g, 85% yield) was obtained.(d) 2- (2, 3-Dichloro-phenylamino)-4-methoxy-3H-benzoimidazole-5-carboxylic acid methyl ester; 2, 3-Dichloroisothiocyanate (1.0 g) is added drop wise to the diamine (1.0 g) in EtOH (20 cm3) at room temperature under argon. After stirring for 1 hour, N-(3-Dimethylaminopropyl)-N'- ethylcarbodiimide hydrochloride (1.2 g) is added and the resulting mixture is heated using microwave radiation at 120 C. After 12 minutes, the reaction mixture is allowed to cool to room temperature and the resulting solid collected by filtration to give the benzimidazole (1.5 g, 78%) as an off-white solid.

Molecular Weight:196.20
XLogP3:0.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:196.08479225
Monoisotopic Mass:196.08479225
Topological Polar Surface Area:87.6
Heavy Atom Count:14
Complexity:210
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes