[CH2:1]([N:8]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:9]1[CH:10]=[C:11]2[C:16](=[C:17]([F:19])[CH:18]=1)[C:15](=O)[NH:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:30])=O>>[Cl:30][C:15]1[C:16]2[C:11](=[CH:10][C:9]([N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:18][C:17]=2[F:19])[CH:12]=[CH:13][N:14]=1A mixture of 19D (0.622 g, 1.74 mmol) and phosphorous oxychloride (6 mL) was heated at 100° C. for 1.5 h. The reaction mixture was concentrated under reduced pressure and co-evaporated twice with toluene. Ice was added to the residue, followed by sodium hydroxide (1N solution) until the pH was basic. The mixture was extracted with methylene chloride (3×), and the combined organic layers were washed with saturated sodium bicarbonate solution and brine, dried (MgSO4), and dried in vacuo to give 19E (0.583 g, 89%) as a yellow solid.
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