[F:1][C:2]1[N:12]=[CH:11][C:5]2[NH:6][C:7](=O)[N:8]=[CH:9][C:4]=2[CH:3]=1.S(Cl)(Cl)=O.[F:17][C:18]1[CH:19]=[C:20]([CH:32]=[CH:33][CH:34]=1)[CH2:21][N:22]1[C:30]2[C:25](=[CH:26][C:27]([NH2:31])=[CH:28][CH:29]=2)[CH:24]=[N:23]1>CN(C=O)C.CC(N(C)C)=O>[F:1][C:2]1[N:12]=[CH:11][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:31][C:27]3[CH:26]=[C:25]4[C:30](=[CH:29][CH:28]=3)[N:22]([CH2:21][C:20]3[CH:32]=[CH:33][CH:34]=[C:18]([F:17])[CH:19]=3)[N:23]=[CH:24]4)[C:4]=2[CH:3]=1A heterogeneous mixture of 6-fluoropyrido[3,4-d]pyrimidin-4(3H)-one (200) (1.65 g, 10.0 mmol), thionyl chloride (30 mL) and a catalytic amount of DMF (2 drops) was stirred under reflux for 5 h to give a homogeneous mixture. It was evaporated under reduced pressure at 45° C. (bath temperature) to give a light brown solid. To this solid was added a solution of 1-(3-fluorobenzyl)-1H-indazol-5-amine (PCT Int. Appl., 2005058245, 30 Jun. 2005) (2.65 g, 11.0 mmol) in dry DMA (15 mL). The residue of 1-(3-fluorobenzyl)-1H-indazol-5-amine was washed down with more DMA (2×2 mL). The reaction mixture was stirred at room temperature for 65 h. It was poured into water (200 mL). The pH was adjusted to ca. 9 using an aqueous solution of Na2CO3 at room temperature. Petroleum ether (200 mL) was added and stirred at room temperature for 2 h. The petroleum ether layer was decanted. It was repeated once more with petroleum ether (200 mL). The solid was collected by filtration and washed with water (5×25 mL). It was suspended in acetone (80 mL) and stirred at room temperature for 20 min. Water (160 mL) was added and stirred further for 1.5 h. The solid was filtered, dried and finally purified by a silica column (MeOH/dichloromethane: gradient from 0-10%) to give 6-fluoro-N-(1-(3-fluorobenzyl)-1H-indazol-5-yl)pyrido[3,4-d]-pyrimidin-4-amine (202) (3.11 g, 80%) as a pale brown solid, mp 218-221° C.; 1H NMR δ [(CD3)2SO] 10.15 (s, 1H), 8.92 (s, 1H), 8.64 (s, 1H), 8.30 (d, J=1.3 Hz, 1H), 8.28 (br s, 14, 8.19 (poorly resolved d, J=0.7 Hz, 1H), 7.77 (d, J=9.0 Hz, 1H), 7.72 (dd, J=9.0, 1.8 Hz, 1H), 7.42-7.32 (m, 1H), 7.15-7.01 (m, 3H), 5.71 (s, 2H). Anal, Calcd for C21H14F2N6: C, 64.94; H, 3.63; N, 21.64. Found C, 65.21; H, 3.71; N, 21.63.
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