[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13])[C:5]([OH:7])=O.[CH:15]1[CH:16]=[CH:17][C:18]2N(O)N=[N:21][C:19]=2C=1.CCN=C=N[CH2:30][CH2:31][CH2:32][N:33]([CH3:35])C.C[N:37](C=O)C>>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:21]=[C:19]([C:18]3[CH:17]=[C:16]4[C:32](=[CH:31][CH:30]=3)[NH:33][CH:35]=[CH:15]4)[N:37]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13]D4 (7.55 g), HOBT (5.23 g) and EDCI (7.42 g) were dissolved in DMF (88 ml). This mixture was stirred for 10 minutes and then the yellow-orange solid from above (6.16 g) dissolved in DMF (88 ml) was added. The reaction mixture was heated to 80° C. overnight then evaporated and partitioned between EtOAc and H2O. The phases were separated and the aqueous solution extracted with two further portions of EtOAc. The combined organic solutions were dried and evaporated. Part of the crude residue was purified on a 40+M Biotage cartridge, eluting with a 5-30% mixture of EtOAc in hexane. This gave the title compound (1.45 g) as an off-white solid. δH (CDCl3, 400 MHz): 1.45 (6H, d), 4.72 (1H, septet), 6.66-6.69 (1H, m), 7.06 (1H, d), 7.29 (1H, apparent triplet or dd), 7.50 (1H, d), 8.01 (1H, dd), 8.08 (1H, dd), 8.27 (1H, d), 8.49-8.52 (1H, m). MS (ES): C19H16ClN3O2 requires 353; found 354 (MH+). The remaining crude reside was triturated with cold MeOH to give the title compound (3.54 g) as an off white solid. MS data as above.
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