反应详情

Following the procedure described in Example 3(A), Step A, N-benzyl-N-isopropyl-2-(5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-acetamide (Preparation 10) (210 mg, 0.451 mmol) was alkylated with 3-bromomethyl-indazole-1-carboxylic acid tert-butyl ester (150 mg, 0.473 mmol). The reaction was diluted with a pH 6.8 buffer solution and the aqueous solution was washed with EtOAc. The organic solution was washed with brine (3×), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified (2×) by preparative chromatography eluting with 5% acetone in CH2Cl2 followed by medium pressure chromatography eluting with a solvent gradient (2% acetone in CH2Cl2 to 14% acetone in CH2Cl2) to provide 19.1 mg of 3-{6-[(benzyl-isopropyl-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 (CD2Cl2) δ 8.05 (m, 1H), 7.12-7.71 (m, 15H), 7.03 (m, 1H), 6.92 (d, 1H), 5.21 (d) and 4.90 (d, total 1H), 4.61-4.72 (m, 2H), 4.49 (s, 1H), 4.43 (t, 1H), 4.25-4.32 (m, 1H), 3.96-4.15 (m, 2H), 1.61 (d, 9H), 1.16 (dd, 3H), 1.04 (dd, 3H); MS 696.4 (M+1).

1. washthe aqueous solution was washed with EtOAc
2. washThe organic solution was washed with brine (3×)
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified (2×) by preparative chromatography
7. washeluting with 5% acetone in CH2Cl2
8. washeluting with a solvent gradient (2% acetone in CH2Cl2 to 14% acetone in CH2Cl2)