(2-bromoacetyl) 2-bromoacetate

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

Procedure: A solution of bromoacetic anhydride (1.03 g, 4 mmol) in THF (3.0 mL) is added over 30 min to a stirred solution of N-(4-chlorobenzyl)-4-hydroxy-8-(methylamino)-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (308 mg of a 1:1 mixture of compound 9 and 4-chlorobenzylamine), triethylamine (500 mg, 5 mmol) in THF (7.0 mL). After 5 h, methanol (20 mL) and triethylamine (300 mg) are added, and the solution is stirred at room temperature overnight. The solution is evaporated, dissolved in chloroform/methanol, and is applied in chloroform to a silica gel column which is eluted with chloroform and then with 5-10% methanol/chloroform to give the title compound (98 mg) which is precipitated from acetonitrile. The solution is evaporated dissolved in chloroform/methanol is eluted with chloroform

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

Procedure: Bromoacetic anhydride (40 mg) is added to a stirred solution of 8-((benzylamino)methyl)-N-(4-chlorobenzyl)-4-hydroxy-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (Preparation 29, 53 mg) in NMP (0.3 mL). After 30 min, triethylamine (50 mg) is added. The solution is diluted with water and the resulting precipitate is filtered and dried under vacuum to give 44 mg of the title compound. Physical characteristics: HRMS m/z 571.2104 (C32H31ClN4O4). the resulting precipitate is filtered dried under vacuum

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bromoacetic anhydride (280 mg) is added to ethyl 8-amino-4-hydroxy-6-(4-morpholinylmethyl)-3-quinolinecarboxylate (Preparation 2, 330 mg) in DMF (4.0 mL). Triethylamine (400 mg) is added and the reaction is heated for 10 min at 60° C. After 1 h, the DMF is removed and the product is chromatographed on silica gel with 10% methanol as the eluant to give 310 mg of the title compound as a mixture with triethylamine hydrobromide. Physical characteristics: 1H NMR (DMSO-d6) δ1.40, 2.45, 3.56, 3.69, 4.39, 4.88, 7.49, 7.97, 8.34. the DMF is removed the product is chromatographed on silica gel with 10% methanol as the eluant

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bromoacetic anhydride (290 mg) is added to a stirred solution of 8-amino-N-(4-chlorobenzyl)-4-hydroxy-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (Preparation 3, 426 mg) in anhydrous DMF (5.0 mL). After 30 min, triethylamine (100 mg) and additional bromoacetic anhydride (100 mg) are added. After 1 h, triethylamine (300 mg) is added and the solution is heated briefly at 80° C. Methanol (8 mL) is added and the resulting precipitate is filtered off, washed with water and dried to afford 262 mg of the title compound as a DMF solvate. Physical characteristics: 1H NMR (DMSO-d6) δ2.37, 2.73, 2.89, 3.53, 3.57, 4.56, 5.11, 7.23, 7.35, 7.40, 7.72, 7.95, 8.72, 10.35, 11.2. After 1 h the resulting precipitate is filtered off washed with water dried