Cl[C:2]1[CH:7]=[C:6]([O:8][C@H:9]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[N:21]2[CH:25]=[CH:24][C:23]([CH3:26])=[N:22]2)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([S:27]([CH3:30])(=[O:29])=[O:28])[N:3]=1.[CH2:31]1[C:35]2([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH2:34][CH:33]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[N:32]1[C:46]([O:48][CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[O:47].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([C@@H:9]([O:8][C:6]2[N:5]=[C:4]([S:27]([CH3:30])(=[O:29])=[O:28])[N:3]=[C:2]([N:38]3[CH2:37][CH2:36][C:35]4([CH2:31][N:32]([C:46]([O:48][CH2:49][C:50]5[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=5)=[O:47])[C@H:33]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:34]4)[CH2:40][CH2:39]3)[CH:7]=2)[C:10]([F:12])([F:13])[F:11])=[C:15]([N:21]2[CH:25]=[CH:24][C:23]([CH3:26])=[N:22]2)[CH:16]=1To a solution of 4-chloro-6-[(1R)-1-[4-chloro-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-methylsulfonylpyrimidine (2.49 g, 5.17 mmol) in dioxane (100 mL) was added 2-benzyl 3-ethyl 2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (1.8 g, 5.2 mmol), Cs2CO3 (5.06 g, 15.5 mmol), and the reaction mixture was heated to 100° C. for 1.5 h. The reaction mixture was cooled to RT, quenched with brine, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification on a 120 g Isco RediSep silica cartridge (EtOAc:heptane) provided (S)-2-benzyl 3-ethyl 8-(6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-(methylsulfonyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as a white solid (1.3 g) in addition to (S)-2-benzyl 3-ethyl 8-(4-chloro-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate.
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