Cl.O1CCOCC1.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([NH:23][C:24]([C:26]2([NH:41]C(=O)OC(C)(C)C)[CH2:31][CH2:30][N:29]([C:32]3[C:33]4[CH:40]=[CH:39][NH:38][C:34]=4[N:35]=[CH:36][N:37]=3)[CH2:28][CH2:27]2)=[O:25])[CH2:16][CH2:17][NH:18][S:19]([CH3:22])(=[O:21])=[O:20])=[CH:11][CH:10]=1.C(O)(C(F)(F)F)=O>>[NH2:41][C:26]1([C:24]([NH:23][CH:15]([C:12]2[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=2)[CH2:16][CH2:17][NH:18][S:19]([CH3:22])(=[O:20])=[O:21])=[O:25])[CH2:27][CH2:28][N:29]([C:32]2[C:33]3[CH:40]=[CH:39][NH:38][C:34]=3[N:35]=[CH:36][N:37]=2)[CH2:30][CH2:31]1HCl (4M) in 1,4-Dioxane (1.615 mL, 6.46 mmol) was added to tert-butyl 4-(1-(4-chlorophenyl)-3-(methylsulfonamido)propylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 117) (261 mg, 0.43 mmol), The resulting suspension was stirred at 20° C. for 1 hour. No reaction. TFA (1 mL) was then added to the reaction and stirred for 16 hours. The reaction was vacuumed to dryness and was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 0.35M NH3/MeOH and pure fractions were evaporated to dryness to afford crude material. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing [AP-HPLC Buffer]) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 4-amino-N-(1-(4-chlorophenyl)-3-(methylsulfonamido)propyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (142 mg, 65.2%) as a white solid.
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