6-Chloro-4-(5-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-2-ylamino)-2-methyl-2H-pyridazin-3-one → 6-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[5-(5-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one

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Reaction Steps

6-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[5-(5-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one was prepared using the general procedure described in example 41 substituting 6-Chloro-4-(5-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-2-ylamino)-2-methyl-2H-pyridazin-3-one for 6-chloro-2-methyl-4-(5-((4-methylpiperazin-1-yl)methyl)pyridin-2-ylamino)pyridazin-3(2H)-one in step 3. For the Suzuki reaction, potassium (2-(acetoxymethyl)-3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)trifluoroborate (Eq: 1.2) was used in place of 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate. After removal of the acetate protecting group using potassium carbonate in methanol, water was added dropwise and the reaction was stirred at room temperature overnight. The solid that formed was filtered, washed with water then ether and dried in a vacuum oven to give 52 mgs of a crystalline white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.38 (s, 9H) 2.13 (s, 3H) 2.47 (s, 2H) 3.22 (s, 3H) 3.39-3.49 (m, 4H) 3.79 (s, 3H) 4.43 (br. s., 2H) 4.58 (br. s., 1H) 7.41-7.65 (m, 5H) 7.75 (d, J=13.22 Hz, 1H) 7.87 (s, 1H) 8.17 (s, 1H) 8.46-8.59 (m, 2H) 9.40 (s, 1H). MS: (M+H)+=628.

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