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0 °C

To a solution of N-isopropyl-N-(6-methoxy-pyridin-3-yl)-2-(5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-acetamide (Preparation 11) (520 mg, 1.079 mmol) in DMF (10 mL) at 0° C. was added NaH (60% in oil, 50 mg, 1.27 mmol). The reaction was stirred at 0° C. for 45 minutes and 3-bromomethyl-indazole-1-carboxylic acid tert-butyl ester (423 mg, 1.36 mmol) in DMF (5 mL) was added. The reaction was stirred at room temperature for 24 hours and was diluted with brine. The aqueous solution was washed with EtOAc (3×). The combined organic solutions were washed with brine (1×), dried (MgSO4), filtered and concentrated in vacuo to provide 3-(6-{[isopropyl-(6-methoxy-pyridin-3-yl)-carbamoyl]-methyl}-5-oxo-1-phenyl-5,6-dihydro-4H-2,3,6,10b-tetraaza-benzo[e]azulen-4-ylmethyl)-indazole-1-carboxylic acid tert-butyl ester. 1H NMR (CD3OD) δ 8.05 (d, 1H), 6.80-7.75 (m, 15H), 4.75 (m) and 4.60 (t, total 3H), 3.85-4.20 (m, 6H), 1.65 (m, 9H), 0.98 (m, 6H); MS 713.6 (M+1), 711.5 (M−1).

1. stirringThe reaction was stirred at room temperature for 24 hours
2. washThe aqueous solution was washed with EtOAc (3×)
3. washThe combined organic solutions were washed with brine (1×)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo