* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Compound 2 (350 g, 2.44 mol) and p-toluenesulfonic acid monohydrate (46.5 g, 0.244 mol) were added to triethyl orthoformate (2100 g, 14.2 mol) and refluxed for 5 hours.After completion of the reaction by TLC, the reaction solution was concentrated and the crude product was quickly purified by column to give Compound 3 (222 g, 1.45 mol). (Yield 59percent) NMR spectrum is shown in FIG. 2.
Compound 2 (350 g, 2.44 mol) and p-toluenesulfonic acid monohydrate (46.5 g, 0.244 mol) were added to triethyl orthoformate (2100 g, 14.2 mol) and refluxed for 5 hours.After completion of the reaction by TLC, the reaction solution was concentrated and the crude product was quickly purified by column to give Compound 3 (222 g, 1.45 mol). (Yield 59%) NMR spectrum is shown in FIG. 2.
58%
In methanol; for 3.0h;Reflux;
A solution of 6-Chloropyridine-2, 3-diamine (718 mg, 5 mmol) in Methanol (10 ml) and Trietyhl orthoformate (10 ml) was heated to reflux for 3 hours. The volatiles were evaporated and the residue was purified by flash chromatography on silica using a CHCl3-MeOH gradient. Yield: 540 mg (58%); ESI-MS m/z 151.1 [M+H]+
Stage B 5-chloro-1H-imidazo[4,5-b]pyridine A solution containing 5.16 g of the product of the preceding stage and 50 ml of formic acid is taken to reflux for 16 hours. The product obtained is impasted in ethyl ether and separated. The product obtained is put into 60 ml of a 2N aqueous solution of soda. The aqueous phase is extracted with an ethyl acetate tetrahydrofuran mixture 80-20 and washed with salt water. The organic phases are combined, dried over anhydrous sodium sulphate, filtered and brought to dryness. In this way 2 g of sought product is isolated M.p.=226~280 C. 0.79 g of sought product is obtained from the mother liquors M.p.=225~27 C.
7
[ 100-60-7 ]
[ 52090-89-8 ]
7-chloro-1H-imidazo[4,5-b]pyridine[ No CAS ]
N-cyclohexyl-N-methyl-1H-imidazo[4,5-b]pyridin-7-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
at 200.0℃; for 2.0h;Microwave apparatus;
Example 209To a 1:1 mixture (lOOmg) of 7-chloro-lH-imidazo [4, 5-b] pyridine and 5-chloro-lH-imidazo [4, 5-b] pyridine was addedN-methylcyclohexanamine (500 ul) , and irradiated microwave at 2000C for 2hours . The reaction mixture was diluted with chloroform, washed with brine, dried over MgSO4 and evaporated. The residue was purified by flash column chromatography over NH-silica gel with a chloroform / EtOAc (100:1-100:5) as eluant to give N-cyclohexyl-N-methyl- EPO <DP n="127"/>lH-imidazo[4,5-b]pyridin-7-amine (54.8mg) as a white solid. 1H-NMR (DMSO-d6) delta:1.03-1.87 (1OH,m) , 2.99 (3H, s) , 5.17-5.41 (IH,m) ,6.2 7(lH,d, J=5.9Hz),7.87(lH,d, J=5.9Hz) , 8.03 (IH, s) , 12.54 (IH, b.s) .? MS(ESI) :m/z 231 (M+H)+.
With acetic acid; 3-chloro-benzenecarboperoxoic acid; at 20.0℃; for 6.0h;
Compound 3 (200 g, 1.3 mol) was dissolved in 1500 ml of acetic acid and then m-chloroperoxybenzoic acid (448.5 g, 2.6 mol) was added and reacted at room temperature for 6 hours.After completion of the reaction by TLC, the reaction mixture was filtered, and the residue was washed with ether to give crude compound 4 (220 g). (Yield 99%)
benzyl-(1H-imidazo[4,5-b]pyridine-5-yl)-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
24%
With tris-(dibenzylideneacetone)dipalladium(0); lithium hexamethyldisilazane; DavePhos; In tetrahydrofuran; at 65.0℃; for 18.0h;Inert atmosphere;
5-Chloro[4,5-b]pyridine (207 mg, 1.1 mmol, 1 eq), DavePhos (10 mg, 0.0264 mmol, 0.25 eq) and Pd2(dba)3 (9 mg, 0.011 mmol, 0.1 eq) were dissolved in dry THF (15 ml) under Argon atmosphere. LiN(TMS)2 (1 M in THF, 2.4 ml, 2.4 mmol, 2.2 eq) and benzylamine (144 pi, 1.3 mmol, 1.2 eq) were added and the mixture was stirred at 65C for 18 h. After cooling to room temperature the mixture was acidified by means of aqueous HCI (5 N) and stirring was continued for further 10 min. The reaction mixture was poured into saturated aqueous NaHCCb and extracted with EtOAc (3x25 ml). The combined organic layers were dried over MgCCb and evaporated to dryness. The residue was purified by semi-preparative HPLC. Yield: 90 mg (24%); MS m/z: 225.2 [M+H]+; HPLC (Gradient A): rt 8.93 min, 100 %; 1H-NMR (DMSO-d6) d: 4.55 (s, 2H); 6.80 (d, 1 H, 3J=8.8 Hz); 7.22-7.27 (m, 1 H); 7.30-7.37 (m, 4H); 7.83-7.91 (m, 2H); 9.08 (s, 1 H)