Ethyl 6-aminoimidazo[1,2-a]pyridine-2-carboxylate

A solution of 250mg (1.01 mmol) of ethyl 6-ni-troimidazo[ 1 , 2-a]pyridine-2-carboxylate in 20 ml of ethanolwas hydrogenated in the presence of 30 mg of palladium(10percent on activated carbon) at RT and standard pressure for5 h. The reaction mixture was then filtered through Celiteand the residue was washed with ethanol. The combinedfiltrates were concentrated under reduced pressure and dried.Yield: 215 mg (quant.)10502] LC/MS [Method 5]: R=1.40 mm; MS (ESIpos):mlz=206 (M+H), 10503] ‘H-NMR (400 MHz, DMSO-d5): ö [ppm]=8.33 (s, 1H), 7.66 (s, 1H), 7.37 (d, 1H), 6.94 (dd, 1H), 5.11 (s, 2H), 4.26 (q, 2H), 1.29 (t, 3H).A suspension of ethyl 6-nitroimidazo[1, 2-a]pyridine-2-carboxylate (20) (20 g, 85 mmol) in MeOH (200 ml) was cooled to 0 °C, 12M hydrogen chloride (70 ml, 850 mmol) was added drop wise followed by portion wise addition of zinc (22.3 g, 340 mmol). The reaction mixture was stirred for 30 minutes.Next, MeOH (140 ml) was added and the reaction was quenched with concentrated NH3(15 equiv.) and filtered. The solid residue was washed with MeOH (2 x 25 ml). The filtratewas concentrated and re-suspended in CHC13 (700 ml), H20 (300 ml) and concentrated NH3(300 ml, 35percent solution). This mixture was stirred until everything was dissolved. The layerswere separated and the water layer was extracted once with CHC13. The organic layers werecombined, washed with a saturated aqueous NaC1 solution (50 ml), dried over MgSO4, filtered and concentrated in vacuo to yield ethyl 6-aminoimidazo [1 , 2-a]pyridine-2-carboxylate (21) (11.8 g, 68percent) as a grey/green solid. UPLC-MS confirmed that the desired product was obtained.Ethyl 6-nitroimidazo[l, 2-α]pyridine-2-carboxylate (1.137 g, 4.83 mmol) and 10percent Pd on C (200 mg) were suspended in EtOH (4 mL). The reaction mixture was stirred at room temperature under 1 atm of hydrogen for 18 h. It was filtered through a pad of Celite and the filtrate was concentrated under reduced pressure. The resulting residue was purified by chromatography to afford ethyl 6-aminoimidazo[l , 2-α]pyridine-2-carboxylate as a green solid (478 mg, yield: 48percent). To a solution of ethyl 6-aminoimidazo[l, 2-a]pyridine-2-carboxylate (A35, 1.0 g, 4.87 mmol) in pyridine (10 mL), benzenesulfonyl chloride (2, 0.75 mL, 5.84 mmol) was added and the resulting solution was stirred at room temperature for 16 h. After completion, the reaction mixture was concentrated under reduced pressure to get crude. The crude was dissolved in DCM and washed with water and dried with anhydrous Na2S04, filtered and concentrated under reduced pressure. The crude was purified by column chromatography using silica gel (100-200 mesh) 0-80% EtOAc/n-hexanes as the eluent to afford ethyl 6-(phenylsulfonamido)imidazo[l, 2-a]pyridine-2-carboxylate 3 as a Light green solid. Yield: 1.20 g (71%) LC-MS (ES) m/z : 346.08 [M+H]+.To a solution of benzoic acid (1, 0.35 g, 2.92 mmol) in DMF (10 mL) was added DIPEA (1.27 mL, 7.31 mmol) followed by HATU (1.01 g, 2.68 mmol). The reaction mixture was stirred for 10 min followed by addition of ethyl 6- aminoimidazo[l, 2-a]pyridine-2-carboxylate (A35, 0.50 g, 2.43 mmol). The reaction mixture was stirred at room temperature for 16 h. After completion, the reaction mixture was diluted with ethyl acetate and water. The organic layer was washed with water, brine solution, dried over anhydrous Na2S04 and concentrated under reduced pressure. The obtained crude was purified by column chromatography using 10% methanol in dichloromethane as eluent to afford the desired product ethyl 6-benzamidoimidazo[l, 2- a]pyridine-2-carboxylate 2 as white solid. Yield: 0.44 g, (58%). LC-MS (ES) m/z : 310.10 [M+H]+To a solution of ethyl 6-aminoimidazo[l, 2-a]pyridine-2-carboxylate(A35, 1.0 g, 4.87 mmol) in pyridine(10 mL) methane sulphonyl chloride(0.37 mL, 4.87 mmol) was added and the resulting solution was stirred at room temperature for 2 h. After completion of reaction concentrated under reduced pressure to get crude. The crude was dissolved in DCM and washed with water and dried with anhydrous Na2S04, filtered and concentrated to afford ethyl 6-(methylsulfonamido)imidazo[l, 2-a]pyridine-2-carboxylate 1-56 as a Light green solid. Yield: 0.70 g(crude) LC-MS(ES) m/z : 284.08[M+H]+.To a solution of ethyl 6-aminoimidazo[l, 2-a]pyridine-2-carboxylate(A35, 0.50 g, 2.43 mmol) in DCM(10 mL) at 0 C was added TEA(1.01 mL, 7.31 mmol) and acetyl chloride(0.26 mL, 3.65 mmol) was added and the resulting solution was stirred at room temperature for 4 h. after completion of reaction diluted with DCM and washed with water the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford compound ethyl 6-acetamidoimidazo[l, 2-a]pyridine-2-carboxylate 1-55 as a brown solid. Yield: 0.40 g(66%) LC-MS(ES) m/z : 248.11[M+H]+.

Molecular Weight:205.21
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:205.085126602
Monoisotopic Mass:205.085126602
Topological Polar Surface Area:69.6
Heavy Atom Count:15
Complexity:247
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes