[NH2:1][C:2]1[C:3]([NH:23][CH2:24][CH3:25])=[CH:4][C:5]([O:8][C:9]2[CH:10]=[C:11]([NH:15]C(=O)OC(C)(C)C)[CH:12]=[CH:13][CH:14]=2)=[N:6][CH:7]=1.[C:26]([CH2:28][C:29](OCC)=O)#[N:27].[N:34]([O-:36])=O.[Na+].[OH-].[Na+].[NH2:40]O>CO.Cl.O>[NH2:15][C:11]1[CH:10]=[C:9]([O:8][C:5]2[N:6]=[CH:7][C:2]3[N:1]=[C:29]([C:28]4[C:26]([NH2:40])=[N:27][O:36][N:34]=4)[N:23]([CH2:24][CH3:25])[C:3]=3[CH:4]=2)[CH:14]=[CH:13][CH:12]=1
The product from Step 3 (0.81 g, 2.3 mmol) and ethyl cyanoacetate (0.52 g, 4.6 mmol) were heated together at 195° C. for 25 minutes. After cooling the mixture to rt, the residue was dissolved in methanol (0.8 mL) and 5N hydrochloric acid (3 mL). The resulting mixture was treated portionwise with sodium nitrite (0.32 g, 4.6 mmol) and stirred at room temperature for 90 minutes. The pH of the mixture was adjusted to 11 by addition of 50% sodium hydroxide solution and a 50% solution of hydroxylamine in water (1.6 mL) was added. The mixture was heated at 110° C. for 16 h and the reaction allowed to cool to rt. The mixture was partitioned between ethyl acetate and water, then the organic phase was washed with brine and evaporated in vacuo. The residue was purified by HPLC to afford the title compound (0.12 g, 15%). MS (ES+) m/e 338 [M+H]+.
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