N-(2-氯乙酰基)甲酯基甲酰胺

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-chloro-5-(phenylsulfinyl)pyridine (2.37 g., .01 mole) in 10 ml. of hexamethylphosphoramide is treated with 2.2 g. of methylchloroacetylcarbamate. The solution is warmed to 50° C for 1 hour, cooled, combined with 5 ml. of methanol and saturated with anhydrous ammonia. The mixture is warmed at 100° C for 3 hours. After cooling, the reaction mixture is diluted with 5 volumes of ether and the crude product is collected by filtration. Recrystallization from hot methanol yields 2-(methoxycarbonylamino)-5-(phenylsulfinyl) imidazo [1,2-a] pyridine, m.p. 249°-251° C. cooled The mixture is warmed at 100° C for 3 hours After cooling the crude product is collected by filtration Recrystallization from hot methanol

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-(6-Amino-1,6-dihydro-pyridazin-4-yl)-N-methyl-benzamide (Intermediate A—Step E) (1 eq, 2.74 mmol, 735 mg) is added to a solution of methyl (chloroacetyl)carbamate (1.2 eq, 3.28 mmol, 498 mg) in DMF (30 ml) and the reaction mixture is stirred at 110° C. for 7.5 h. The solvent is then removed in vacuo and the product is purified by flash column chromatography eluting with 9:1 DCM/MeOH to afford [7-(3-Methylcarbamoyl-phenyl)-imidazo-[1,2-b]-pyridazin -2-yl]-carbamic acid methyl ester as a green solid; [M+H]+=326 The solvent is then removed in vacuo the product is purified by flash column chromatography eluting with 9:1 DCM/MeOH

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Reaction of 2-amino-5-(2-pyridyloxy) pyridine with methyl chloroacetylcarbamate as in Example 3 yields 2-(methoxycarbonylamino)-6-(2-pyridyloxy) imidazo [1,2-a] pyridine.

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-chloro-5-(phenylsulfinyl)pyridine (2.37 g., .01 mole) in 10 ml. of hexamethylphosphoramide is treated with 2.2 g. of methylchloroacetylcarbamate. The solution is warmed to 50° C for 1 hour, cooled, combined with 5 ml. of methanol and saturated with anhydrous ammonia. The mixture is warmed at 100° C for 3 hours. After cooling, the reaction mixture is diluted with 5 volumes of ether and the crude product is collected by filtration. Recrystallization from hot methanol yields 2-(methoxycarbonylamino)-5-(phenylsulfinyl) imidazo [1,2-a] pyridine, m.p. 249°-251° C. cooled The mixture is warmed at 100° C for 3 hours After cooling the crude product is collected by filtration Recrystallization from hot methanol

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-amino-5-(methylsulfonyl)pyridine (58.7 mmol) and methyl(chloroacetyl)carbamate (70 mmol) in 88 ml of HMPT is treated in a manner similar to that described above with respect to Example 1D to yield the product. is treated in a manner similar to to yield the product

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-amino-5-(methylsulfinyl)pyridine (7.9 mmol) and methyl(chloroacetyl)carbamate (11.6 mmol) in 12 ml of HMPT is treated in a manner similar to that described in Example 1D to yield the product. is treated in a manner similar to to yield the product

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-amino-5-(methylthio)pyridine (0.667 mol) and methyl(chloroacetyl)carbamate (0.667 mol) in 325 ml of HMPT is heated at 100° C. for 5 hours. After dilution with 2000 ml of H2O, the product is collected by filtration, successively washed with H2O, MeOH and CH2Cl2, and dried. After dilution with 2000 ml of H2O, the product is collected by filtration successively washed with H2O, MeOH and CH2Cl2 dried

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-chloroacetamide (122.6 g, 1.31 mol) in 300 ml of 1,2-dichloroethane is cooled to 0° C. and treated with oxalyl chloride (200 g, 1.57 mol). The reaction mixture is heated at reflux for 4 hours. After cooling to 5° C., 68 ml of MeOH is added dropwise while keeping the internal temperature below 15° C. with external cooling. After addition is complete, the product is separated by filtration and washed with CH2Cl2 and Et2O. Recrystallization from CH2Cl2 yields methyl(chloroacetyl)carbamate. The reaction mixture is heated at reflux for 4 hours After cooling to 5° C. the internal temperature below 15° C. After addition the product is separated by filtration washed with CH2Cl2 and Et2O Recrystallization from CH2Cl2

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-amino-5-(methylsulfonyl)pyridine (58.7 mmol) and methyl(chloroacetyl)carbamate (70 mmol) in 88 ml of HMPT is treated in a manner similar to that described above with respect to Example 1D to yield the product. is treated in a manner similar to to yield the product

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-amino-5-(methylsulfinyl)pyridine (7.9 mmol) and methyl(chloroacetyl)carbamate (11.6 mmol) in 12 ml of HMPT is treated in a manner similar to that described in Example 1D to yield the product. is treated in a manner similar to to yield the product

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-amino-5-(methylthio)pyridine (0.667 mol) and methyl(chloroacetyl)carbamate (0.667 mol) in 325 ml of HMPT is heated at 100° C. for 5 hours. After dilution with 2000 ml of H2O, the product is collected by filtration, successively washed with H2O, MeOH and CH2Cl2, and dried. After dilution with 2000 ml of H2O, the product is collected by filtration successively washed with H2O, MeOH and CH2Cl2 dried

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-chloroacetamide (122.6 g, 1.31 mol) in 300 ml of 1,2-dichloroethane is cooled to 0° C. and treated with oxalyl chloride (200 g, 1.57 mol). The reaction mixture is heated at reflux for 4 hours. After cooling to 5° C., 68 ml of MeOH is added dropwise while keeping the internal temperature below 15° C. with external cooling. After addition is complete, the product is separated by filtration and washed with CH2Cl2 and Et2O. Recrystallization from CH2Cl2 yields methyl(chloroacetyl)carbamate. The reaction mixture is heated at reflux for 4 hours After cooling to 5° C. the internal temperature below 15° C. After addition the product is separated by filtration washed with CH2Cl2 and Et2O Recrystallization from CH2Cl2