C(Cl)(=O)C(Cl)=O.[Br:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[C:15]([C:18]([OH:20])=O)[CH:14]=[CH:13]2.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.CCN(CC)CC>C(Cl)Cl.CN(C=O)C>[Br:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[C:15]([C:18]([N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)=[O:20])[CH:14]=[CH:13]2
At 0° C., oxalyl chloride (2.0 M solution in DCM, 2.73 mL, 5.47 mmol) was added to a suspension of 8-bromoquinoline-2-carboxylic acid (Princeton BioMolecular Research, Monmouth Junction, N.J.; 690 mg, 2.74 mmol) in 5 mL of DCM followed by 3 drops of DMF. The heterogeneous mixture was stirred at RT for 1 h, and it became homogeneous. The volatiles were removed in vacuo, and the residual brown solid was dissolved in 10 mL of DCM and cooled with an ice bath. Morpholine (0.29 mL, 3.28 mmol) and Et3N (0.46 mL, 3.28 mmol) were added. The reaction was stirred at RT for 1 h. The mixture was then diluted with 50 mL of DCM, washed sequentially with 5 mL of 0.5 N HCl, 5 mL of water, 5 mL of 0.5 N NaOH and 5 mL of brine. The DCM solution was dried over Na2SO4 and concentrated to give a brown oil. Re-crystallization from ether/hexanes gave (8-bromoquinolin-2-yl)(morpholino)methanone (855 mg, 97% yield) as a tan crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.60 (1H, d, J=8.6 Hz), 8.22 (1H, m), 8.10 (1H, d, J=8.0 Hz), 7.86 (1H, d, J=8.4 Hz), 7.61 (1H, t, J=7.8 Hz), 3.79 (4H, br.), 3.69 (4H, br). m/z (ESI, +ve) 321/323 (M+H)+.
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