1H-Benzimidazol-7-amine

4- Nitro-lH-benzimidazole was hydrogenated (48 psi) with 1 g 10percent Pd/C in HOAc (100 mL) for 3 h. The crude mixture was filtered through a pad of Celite, washing with MeOH, and concentrated. The residue was taken up in 2 M aq HCl and applied to a Phenomenex Strata-X-C ion exchange column (5 g). The column was washed with H20 and MeOH, The washings contained additional material and were applied to another Strata X-C ion exchange column ( 5g). The columns were washed with H20 and MeOH. Each of the columns containing product were washed separately with 10percent concentrated NH4OH in MeOH and the product collected in fractions. The collected fractions were concentrated to give lH-Benzimidazol-4-amine as a deep red solid. 1H NMR (500 MHz, d6-DMSO) delta 12.10 (bs, 1 H), 7.98 (s, 1 H), 6.87 (t, J = 7.81 Hz, 1 H), 6.72 (d, J = 7.82 Hz, 1 H), 6.34 (d, J = 7.57 Hz, 1 H), 5.16 (bs, 2 H).Typical examples of the benzimidazole derivative represented by the general formula (8) above are listed below: 4-hydroxybenzimidazol, Then, cooling and collection yielded the 4-nitro-benzimidazole product by filtration. Catalytic reduction using Raney Nickel in ethanol under 1 atm of hydrogen for 1 h gave 1H-benzoimidazol-4-ylamine as an air sensitive solid) and 4-formyl-piperidine-1-carboxylic acid benzyl ester (prepared from 4-(N-methoxy-N-methyl-carbamoyl)-piperidine-1-carboxylic acid benzyl ester, using the procedures described by S. Nahm and S. W. Weinreb, Tetrahedron Letters, 22:3815-3818(1981)) on a 1 mmol scale by reductive amination in 5 mL of 1, 2-dichloromethane using sodium triacetoxyborohydride over 0.5 of Raney Nickel under 1 atm of hydrogen for 1 h, followed by immediate conversion of the crude, air sensitive triaminopyridine into the imidazo[4, 5b]pyridine by heating with 51 mL of 96% formic acid and 2 mL of 37% hydrochloric acid at reflux overnight.Adenine (17.4 g, 0.13 mol), Potassium carbonate (21.5 g, 0.15 mol), R-propylene carbonate (15.8 g, 0.15 mol)Was dissolved in 50 mL of N, N-dimethylformamide, Heated to 90 ~ 125 C, Insulation at 90 ~ 125 CReaction 3 ~ 6 hours;Down to room temperature, Under argon, magnesium isopropoxide (15.7 g, 0.14 mol) was added, Heating up to 30 ~ 45, Insulation reaction 0.5 ~ 1 hour;Dimethyl p-toluenesulfonyloxymethylphosphonate (44.1 g, 0.15 mol) was added dropwise, Insulation at 30 ~ 45 C continue to react 4 ~ 6 hours; the system down to room temperature, The reaction system was concentrated under reduced pressure to give a viscous oily substance intermediate 2;To the resulting intermediate 2 was added 124 g of concentrated hydrochloric acid, Heating up to 90 ~ 110 C, Insulation reaction 3 ~ 6 hours;Down to room temperature, The reaction was continued at room temperature for 1 to 2 hours, Filter, The filter cake was washed twice with 150 mL of 5 wt% dilute aqueous hydrochloric acid, The filtrate was adjusted with sodium hydroxide solution rhoH- = 2 ~ 3, Crystallization overnight, Cooling to 0 ~ 3 C, So that the crystallization for 3 hours;Filter, The filter cake was washed once with 30 mL of water, 50 mL of water and acetone (V / V = 1: 1) was washed twice, 50mL acetone washed once;Vacuum drying, Tylenolide28g, The total molar yield was 75.7%HPLC purity was 98.2%.Adenine (17.4 g, 0.13 mol), Potassium carbonate (21.5 g, 0.15 mol), R-propylene carbonate (15.8 g, 0.15 mol)Was dissolved in 50 mL of N, N-dimethylformamide, Heated to 90 ~ 125 ° C, Insulation at 90 ~ 125 ° CReaction 3 ~ 6 hours;Down to room temperature, Under argon, magnesium isopropoxide (15.7 g, 0.14 mol) was added, Heating up to 30 ~ 45, Insulation reaction 0.5 ~ 1 hour;Dimethyl p-toluenesulfonyloxymethylphosphonate (44.1 g, 0.15 mol) was added dropwise, Insulation at 30 ~ 45 ° C continue to react 4 ~ 6 hours; the system down to room temperature, The reaction system was concentrated under reduced pressure to give a viscous oily substance intermediate 2;To the resulting intermediate 2 was added 124 g of concentrated hydrochloric acid, Heating up to 90 ~ 110 ° C, Insulation reaction 3 ~ 6 hours;Down to room temperature, The reaction was continued at room temperature for 1 to 2 hours, Filter, The filter cake was washed twice with 150 mL of 5 wtpercent dilute aqueous hydrochloric acid, The filtrate was adjusted with sodium hydroxide solution rhoH- = 2 ~ 3, Crystallization overnight, Cooling to 0 ~ 3 ° C, So that the crystallization for 3 hours;Filter, The filter cake was washed once with 30 mL of water, 50 mL of water and acetone (V / V = 1: 1) was washed twice, 50mL acetone washed once;Vacuum drying, Tylenolide28g, The total molar yield was 75.7percentHPLC purity was 98.2percent.Adenine (17.4 g, 0.13 mol), Sodium carbonate (15.9 g, 0.15 mol)1R-propylene carbonate (15.8 g, 0.15 mol)Was dissolved in 50 mL of N-methylpyrrolidone, Heated to 90 ~ 125 C, Insulation at 90 ~ 125 CReaction 3 ~ 6 hours;Down to room temperature, Under a argon atmosphere, magnesium tert-butoxide (23.8 g, 0.14 mol) was added, Heating up to 30 ~ 45, Insulation reaction 0.5 ~ 1 hour;DripP-toluenesulfonyloxymethylphosphonic acidDiethyl ester (48.3 g, 0.15 mol)Insulation at 30 ~ 45 C continue to react 4 ~ 6 hours; the system down to room temperature, The reaction system was concentrated under reduced pressure to give a viscous oily substance intermediate 2;To the resulting intermediate 2 was added 130 g of concentrated sulfuric acid, Heating up to 90 ~ 110 C, Insulation reaction 3 ~ 6 hours;Down to room temperature, The reaction was continued at room temperature for 1 to 2 hours, Filter, The filter cake was washed twice with 150 mL of 5 wt% dilute sulfuric acid aqueous solution, The filtrate with sodium hydroxide solution rhoEta = 2 ~ 3, Crystallization overnight, cooling to 0 ~ 3 C, So that the crystallization for 3 hours;Filter, The filter cake was washed once with 30 mL of water, 50 mL of water and acetone (V / V = 1: 1) was washed twice, 50mL acetone washed once;Vacuum drying, Tylenolide 31g, The total molar yield was 83.8%HPLC purity of 98.5%Adenine (17.4 g, 0.13 mol), Sodium carbonate (15.9 g, 0.15 mol)1R-propylene carbonate (15.8 g, 0.15 mol)Was dissolved in 50 mL of N-methylpyrrolidone, Heated to 90 ~ 125 ° C, Insulation at 90 ~ 125 ° CReaction 3 ~ 6 hours;Down to room temperature, Under a argon atmosphere, magnesium tert-butoxide (23.8 g, 0.14 mol) was added, Heating up to 30 ~ 45, Insulation reaction 0.5 ~ 1 hour;DripP-toluenesulfonyloxymethylphosphonic acidDiethyl ester (48.3 g, 0.15 mol)Insulation at 30 ~ 45 ° C continue to react 4 ~ 6 hours; the system down to room temperature, The reaction system was concentrated under reduced pressure to give a viscous oily substance intermediate 2;To the resulting intermediate 2 was added 130 g of concentrated sulfuric acid, Heating up to 90 ~ 110 ° C, Insulation reaction 3 ~ 6 hours;Down to room temperature, The reaction was continued at room temperature for 1 to 2 hours, Filter, The filter cake was washed twice with 150 mL of 5 wtpercent dilute sulfuric acid aqueous solution, The filtrate with sodium hydroxide solution rhoEta = 2 ~ 3, Crystallization overnight, cooling to 0 ~ 3 ° C, So that the crystallization for 3 hours;Filter, The filter cake was washed once with 30 mL of water, 50 mL of water and acetone (V / V = 1: 1) was washed twice, 50mL acetone washed once;Vacuum drying, Tylenolide 31g, The total molar yield was 83.8percentHPLC purity of 98.5percent

Molecular Weight:133.15
XLogP3:0.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:133.063997236
Monoisotopic Mass:133.063997236
Topological Polar Surface Area:54.7
Heavy Atom Count:10
Complexity:126
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes