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Stage #1: With boron tribromide In dichloromethane at 0 - 20℃; for 72h;
Stage #2: With water; sodium hydroxide In dichloromethane Cooling; |
2.1.3 Example 2-1-1 Preparation of 2-{4-[(3-{4-[(3-chloropyridin-4-yl)amino]-5-methoxypyrimiclin-2-yl}-1 H- indazol-1 -yl)methyl]-3,5-d
General procedure: Example 2-1-1 Preparation of 2-{4-[(3-{4-[(3-chloropyridin-4-yl)amino]-5-methoxypyrimiclin-2-yl}-1 H- indazol-1 -yl)methyl]-3,5-d 177 mg of N-(3-Chloropyridin-4-yl)-2-{1 -[2,6-difluoro-4-(2-methoxyethoxy)benzyl]-1 H- indazol-3-yl}-5-methoxypyrimidin-4-amine 1-9-1 (0.32 mmol, 1.0 eq.) were dissolved in 8.2 mL dichloromethane and cooled down to 0 "C. 1 .0 mL tribromoborane (1 M in dichloromethane, 1 .0 mmol, 3.2 eq.) was slowly added at CC. When all tribromoborane was added, the icebath was removed and the mixture was stirred at rt for 72 h. The reaction mixture was diluted with icewater and DCM and 2-molar sodiumhydroxide- solution was added until pH12. The layers were seperated and the aquoeus layer was extracted with dichloromethane twice. The crude product was purified by flash chromatography to provide the 91 % pure target compounds: 26 mg, which was further purified py HPLC: 100% pure, 7.9 mg, 15 μιηοΙ, 12% 1 H-NMR (400MHz, DMSO-d6): δ [ppm]= 3.68 (q, 2H), 4.01 (t, 2H), 4.08 (s, 3H), 4.88 (t, 1 H), 5.69 (s, 2H), 6.75 - 6.90 (m, 2H), 7.27 (t, 1 H), 7.50 (t, 1 H), 7.85 (d, 1 H), 8.26 (s, 1 H), 8.40 (d, 1 H), 8.43 - 8.54 (m, 2H), 8.65 (s, 1 H), 8.98 (d, 1 H). |