5-METHOXY-1H-BENZOIMIDAZOL-2-YLAMINE

Black Solid

General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).General procedure: O. 5-Bromo-2-aminobenzimidazole (11) 5-Bromo-2-aminobenzimidazole (11) was synthesized according to a modified version of a reported procedure. [31] In brief, 4-bromo-1, 2-diaminobenzene (1.0 g, 5.35 mmol, 1.0 eq.) was dissolved in a 1:1 mixture of MeOH (40 mL) and water (40 mL) in a 250 mL round bottom flask. The reaction mixture was treated with CNBr (1.7 g, 16.04 mmol, 3.0 eq.) and heated at 50° C. for 1 h. After cooling to room temperature, the MeOH was removed in vacuo, and the remaining mixture was basified with 1.0 M aq. NaOH (to pH=8.0) and extracted with EtOAc (3*30 mL).Representative compounds of the present invention are:...5-ethyl-2-aminobenzimidazole;5-methyl-2-aminobenzimidazole;5-chloro-2-aminobenzimidazole;5-fluoro-2-aminobenzimidazole;5-methoxy-2-aminobenzimidazole;5-chloro-6-methyl-2-aminobenzimidazole;5-chloro-6-fluoro-2-aminobenzimidazole;5-methyl-2-guanidinobenzimidazole;...Valuable products which may be prepared by the method of the invention include but are not limited to...1-benzyl-2-hydroxy-4-tolylimidazole1-benzyl-2-hydroxy-5-tolylimidazole2-mercapto-1-(phenylpropyl)imidazole2-aminobenzimidazole2-amino-5-methoxybenzimidazole2-hydroxy-5, 6-dichlorobenzimidazole2-mercapto-6-bromobenzimidazole5-chloro-2-mercapto-6-methoxybenzimidazole...As examples there may be cited:...2-amino-4-chloro-benzimidazole2-amino-5-chloro-benzimidazole2-amino-5, 6-dichloro-benzimidazole2-amino-4-chloro-6-methyl-benzimidazole2-amino-5-methoxy-benzimidazole2-amino-6-ethoxy-benzimidazole2-amino-6-nitro-benzimidazole2-amino-6-cyano-benzimidazole...To 5-methoxy-lH-benzo[According to GP1 , commercially available 5-methoxy-1 /-/-benzimidazol-2-amine (CAS: 6232-91 -3, 85.0 mg, 0.52 mmol), 2-[(4-chlorophenyl)amino]-1 , 3-thiazole-4-carboxylic acid (CAS: 165682-82-6, WO2007/5785 A1 , Bio. Med. Chem. Let, 2013, 23, 4979- 4984, 133 mg, 0.52 mmol), HATU (218 mg, 0.57 mmol) and DIPEA (0.1 ml_, 0.57 mmol) were stirred overnight. Then additionnal DIPEA (181 muIota_, 2 eq.) and HATU (218 mg, 0.57 mmol, 1 eq.) were added to the reaction mixture and the mixture was stirred for further 24 h at RT. After workup, the crude product was purified using preparative HPLC (method 3) and additionnal preparative HPLC (see method below) giving the desired amide 9 (10.2 mg, 80percent purity, 4percent yield) as a yellow solid. 1H-NMR (400 MHz, DMSO- d6) delta [ppm]: 0.851 (0.60), 1 .230 (3.19), 1 .256 (4.15), 1 .295 (1 .47), 1.331 (2.20), 2.518 (2.35), 2.523 (1.62), 3.768 (16.00), 6.744 (1.18), 6.751 (1.18), 6.766 (1 .17), 6.772 (1 .28), 7.034 (0.58), 7.353 (1 .21 ), 7.375 (1.29), 7.381 (3.55), 7.386 (1 .10), 7.398 (1.02), 7.404 (3.77), 7.810 (3.30), 7.815 (1 .02), 7.827 (0.89), 7.832 (3.02), 7.913 (1 .21 ), 10.569 (1 .13); LC-MS (method 2): Rt = 1 .20 min; MS (ESIpos): m/z = 400 [M+H]+. Preparative HPLC method: Instrument: Waters Acquity UPLCMS SingleQuad; column: Acquity UPLC BEH Ci8 1 .7 muiotaeta, 50x 2.1 mm; eluent A: water + 0.2 vol percent aqueous ammoniac (32percent); eluent B: acetonitrile; gradient: 0-1 .6 min 1 -99percent B, 1 .6-2.0 min 99percent B; flow: 0.8 mL/min; temperature: 60 ; DAD scan: 210-400 nm. (0817) Preparation: Instrument: Waters Autopurificationsystem; column: Waters XBrigde Cis 5.0 muiotaeta 100x30 mm; eluent A: water + 0.2 vol percent aqueous ammoniac (32percent); eluent B: acetonitrile; gradient: 0.00-0.50 min 22percent B (40 to 70 mL/min), 0.51-5.50 min 43-53percent B (70 mL/min), DAD scan: 210-400 nm.General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).

Heterocyclic amine with possible mutagenic properties.

Molecular Weight:163.18
XLogP3:0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:163.074561919
Monoisotopic Mass:163.074561919
Topological Polar Surface Area:63.9
Heavy Atom Count:12
Complexity:164
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes