(2-chloroacetyl) 2-chloroacetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of mannosamine hydrochloride (250 mg, 1.16 mmol) and sodium methoxide (1.16 ml of a 1 M methanolic solution) in dry MeOH (10 ml) was stirred for 1 h at room temperature, after which chloroacetic anhydride (991 mg, 5.80 mmol) was added. The resulting solution was stirred overnight at room temperature under an atmosphere of N2 and then quenched with H2O (5 ml) for 1 hour. The solution was neutralized with saturated NaHCO3 and concentrated, and the residue was filtered through a plug of silica gel eluting with 5:1 CHCl13/MeOH. The crude product obtained was dissolved in DMF (10 ml) and NaN3 (78 mg, 1.39 mmol) was added. After heating at reflux overnight, the solution was cooled and concentrated. Purification by silica gel chromatography eluting with a gradient of 50:1 to 6:1 CHCl3/MeOH afforded 179 mg of compound 20 (59% over two steps). The compound was peracetylated prior to incubation with cells as follows. A solution of 20 (25 mg, 0.095 mmol), acetic anhydride (1.0 ml, 11 mmol) and a catalytic amount of DMAP in pyridine (2 ml) was cooled to 0° C. The mixture was stirred overnight, warmed to rt, then diluted with CH2Cl2 (100 ml) and washed with 1 N HCl (3×50 ml), sat. NaHCO3 (1×50 ml), water (1×50 ml) and saturated NaCl (1×50 ml). The combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by silica gel chromatography eluting with a gradient of 1:10 to 1:2 EtOAc/hexanes to afford 39 mg (95%) of acetylated 20 (compound 36). quenched with H2O (5 ml) for 1 hour concentrated the residue was filtered through a plug of silica gel eluting with 5:1 CHCl13/MeOH The crude product obtained After heating at reflux overnight the solution was cooled concentrated Purification by silica gel chromatography eluting with a gradient of 50:1 to 6:1 CHCl3/MeOH

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(5-(N′-hydroxycarbamimidoyl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide 9 (500 mg, 1.62 mmol) and 2-chloroacetic anhydride (553 mg, 3.23 mmol) in anhydrous 1-methyl-2-pyrrolidinone (10 mL) was heated in the microwave at 110° C. for 12 minutes. The crude was diluted with water and extracted with ethyl acetate. The organic was washed with water/brine mixture and dried over anhydrous sodium sulfate. The crude product was purified by silica chromatography. MS m/z 368.08 (M+1)+. extracted with ethyl acetate The organic was washed with water/brine mixture dried over anhydrous sodium sulfate The crude product was purified by silica chromatography

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(5-(N′-hydroxycarbamimidoyl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (9) (500 mg, 1.62 mmol) and 2-chloroacetic anhydride (553 mg, 3.23 mmol) in anhydrous NMP (10 mL) was heated in the microwave at 110° C. for 12 minutes. The crude was diluted with water and extracted with ethyl acetate. The organic was washed with a water/brine mixture and dried over anhydrous sodium sulfate. The solvent was concentrated and the crude product was purified by silica chromatography to yield N-(5-(5-(chloromethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (38). MS m/z 378.9 (M+1)+. extracted with ethyl acetate The organic was washed with a water/brine mixture dried over anhydrous sodium sulfate The solvent was concentrated the crude product was purified by silica chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-amino-4,6-dimethylpyridine(1.69 g), chloroacetic anhydride(3.54 g), and triethylamine(3.83 ml) were stirred in benzene(30 ml) for 1 hour while being cooled with ice. The reaction mixture, with water added thereto, was extracted with ethyl acetate. The extract was dried over sodium sulfate anhydride and then concentrated under a vacuum. To the solution of the residue in dimethylformamide(23 ml) was added potassium phthalimide(2.82 g) and then the mixture was refluxed with stirring for 3 hours. After a large amount of water was added thereto, the depositing crystals were collected by filtration. The solution of the crystals in ethanol(50 ml), with hydrazine monohydrate(1.34 ml) added thereto, was refluxed with stirring for 3 hours and then concentrated under a vacuum. The residue, with water added thereto, was acidified with sodium hydrogencarbonate and then extracted with ethyl acetate. The extract was dried over sodium sulfate anhydride and then was concentrated under a vacuum. The solution of the residue in tetrahydrofuran(45 ml) was dropped into the suspension of lithium aluminium hydride(0.64 g) in tetrahydrofuran(45 ml) while being cooled with ice and the mixture was stirred at room temperature for 1 hour. A small amount of water was added thereto and then the resulting deposit was filtrated out. The filtrate was concentrated under a vacuum, thereby yielding 1.90 g of the aimed compound. while being cooled with ice was extracted with ethyl acetate The extract was dried over sodium sulfate anhydride concentrated under a vacuum To the solution of the residue in dimethylformamide(23 ml) was added potassium phthalimide(2.82 g) the mixture was refluxed After a large amount of water was added the depositing crystals were collected by filtration The solution of the crystals in ethanol(50 ml), with hydrazine monohydrate(1.34 ml) added was refluxed with stirring for 3 hours concentrated under a vacuum The residue, with water added extracted with ethyl acetate The extract was dried over sodium sulfate anhydride was concentrated under a vacuum The solution of the residue in tetrahydrofuran(45 ml) was dropped into the suspension of lithium aluminium hydride(0.64 g) in tetrahydrofuran(45 ml) while being cooled with ice the mixture was stirred at room temperature for 1 hour A small amount of water was added the resulting deposit was filtrated out The filtrate was concentrated under a vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-amino-2-methoxypyridine(3.18 g), chloroacetic anhydride(6.56 g), and triethylamine(7.09 ml) were stirred in benzene(55 ml) for 1 hour while being cooled with ice. The reaction mixture, with water added thereto, was extracted with ethyl acetate. The extract was dried over sodium sulfate anhydride and then concentrated under a vacuum. To the solution of the residue in dimethylformamide(20 ml) was added potassium phthalimide(5.21 g) and then the mixture was refluxed with stirring for 3 hours. After a large amount of water was added thereto, the depositing crystal was collected by filtration. The solution of the crystal in ethanol(120 ml), with hydrazine monohydrate(2.56 ml) was refluxed with stirring for 2 hours and then concentrated under a vacuum. The residue, with water added thereto, was acidified with sodium hydrogencarbonate and then extracted with ethyl acetate. The extract was dried over sodium sulfate anhydride and then concentrated under a vacuum. The solution of the residue in tetrahydrofuran(40 ml) was dropped into the suspension of lithium aluminium hydride(2.63 g) in tetrahydrofuran(40 ml) while being cooled with ice and the mixture was stirred at room temperature for 2 hours. A small amount of water was added thereto and the resulting deposit was filtrated out. The filtrate was concentrated under a vacuum, thereby yielding 2.12 g of the aimed compound. while being cooled with ice was extracted with ethyl acetate The extract was dried over sodium sulfate anhydride concentrated under a vacuum To the solution of the residue in dimethylformamide(20 ml) was added potassium phthalimide(5.21 g) the mixture was refluxed After a large amount of water was added the depositing crystal was collected by filtration The solution of the crystal in ethanol(120 ml), with hydrazine monohydrate(2.56 ml) was refluxed with stirring for 2 hours concentrated under a vacuum The residue, with water added extracted with ethyl acetate The extract was dried over sodium sulfate anhydride concentrated under a vacuum The solution of the residue in tetrahydrofuran(40 ml) was dropped into the suspension of lithium aluminium hydride(2.63 g) in tetrahydrofuran(40 ml) while being cooled with ice the mixture was stirred at room temperature for 2 hours A small amount of water was added the resulting deposit was filtrated out The filtrate was concentrated under a vacuum

Conditions: temp:0.00; pressure:0.00; stir: