Cl[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:12]=3)=[C:4]2[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C.[CH:89]1([NH2:94])[CH2:93][CH2:92][CH2:91][CH2:90]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[NH:17]([C:13]1[N:12]=[C:11]([C:10]2[C:9]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)=[N:8][N:5]3[CH:6]=[CH:7][C:2]([NH:94][CH:89]4[CH2:93][CH2:92][CH2:91][CH2:90]4)=[CH:3][C:4]=23)[CH:16]=[CH:15][N:14]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1To a solution of 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-phenyl-2-pyrimidinamine (100 mg, 0.24 mmol) in cyclopentylamine (5 mL) was added successively racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (72 mg), cesium carbonate (200 mg), and palladium (II) acetate (16 mg). The resulting mixture was stirred at 100° C. for 24 hours, then additional racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (72 mg) and palladium (II) acetate (16 mg) were added and the reaction stirred at 100° C. for additional 24 hours, at which time the reaction was judged complete by thin layer chromatography. The solution was cooled to room temperature and ethyl acetate and water were added to the reaction mixture. The phases were separated, and the aqueous phase again extracted with ethyl acetate. The combined organic phases were dried (magnesium sulfate), filtered and concentrated. The resulting residue was purified by flash chromatography (1:1 hexanes:ethyl acetate) to give N-[3-(2-anilino-4-pyrimidinyl)-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-5-yl]-N-cyclopentylamine (40 mg, 36%) as a solid. 1H NMR (CDCl3): δ 8.21 (d, 1H), 8.13 (d, 1H), 7.65 (m, 4H), 7.4–7.24 (m, 4H), 7.18 (t, 21H), 7.06 (t, 1H), 6.44 (d 1H), 6.30 (dd, 1H), 4.16 (d, 1H), 3.68 (m, 1H), 1.4–2.2 (m, 8H); 19F-NMR (CDCl3): δ−113.32; MS m/z 466 (M+1).
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