Reaction SMILES: [CH3:1][O:2][C:3]1[CH:49]=[CH:48][C:6]([CH2:7][N:8]([CH2:39][C:40]2[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([C@H:23]([N:25]4[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][C@@H:26]4[CH3:38])[CH3:24])[CH:19]=[N:20][C:21]=3[F:22])[N:10]=2)=[CH:5][CH:4]=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+].CCN(CC)CC.[CH3:69][S:70](Cl)(=[O:72])=[O:71]>C(Cl)Cl.O>[F:22][C:21]1[C:16]([C:11]2[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([N:8]([CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=3)[CH2:7][C:6]3[CH:48]=[CH:49][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[N:10]=2)=[CH:17][C:18]([C@H:23]([N:25]2[CH2:30][CH2:29][N:28]([S:70]([CH3:69])(=[O:72])=[O:71])[CH2:27][C@@H:26]2[CH3:38])[CH3:24])=[CH:19][N:20]=1
Reactant: CS(=O)(=O)Cl
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc([C@@H](C)N4CCN(C(=O)OC(C)(C)C)C[C@@H]4C)cnc3F)n2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc([C@@H](C)N4CCN(S(C)(=O)=O)C[C@@H]4C)cnc3F)n2)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 84 %

Procedure:
A solution of tert-butyl(3S)-4-((1R)-1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoro-3-pyridinyl)ethyl)-3-methyl-1-piperazinecarboxylate (9.17 g, 13.65 mmol) in CH2Cl2 (136 mL) at 0° C. was treated with TFA (52.6 mL, 682 mmol) (added over 10 min). The ice bath was then removed and the reaction mixture stirred at ambient temperature for 90 min. The solvent was removed in vacuo with a heating bath at 25° C., providing a viscous oil, which was cooled to 0° C. and diluted with 150 mL of CH2Cl2. Ice was added to the resulting solution, followed by solid NaHCO3 with rapid stirring until effervescence ceased. The resulting mixture was diluted with water (100 mL) and CH2Cl2 (150 mL). The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (2×). All organic layers were then combined, dried over sodium sulfate, and filtered through a 0.45 μm ZAPCAP filter (Whatman, Schleicher & Schuell). The filtrate was then concentrated to about 150 mL and cooled to 0° C. NEt3 (7.61 mL, 54.6 mmol) was added, followed by methanesulfonyl chloride (2.11 mL, 27.3 mmol). After 1 h at 0° C., saturated aqueous NaHCO3 was added and the resulting mixture was extracted with CH2Cl2 (3×). The combined organic extracts were dried over Na2SO4, filtered, and concentrated. The crude material was loaded onto a silica gel column (330 g) as a solution in CH2Cl2 and purified by column chromatography (20% to 100% (10% MeOH/EtOAc)/hexanes), which gave 4-(2-fluoro-5-((1R)-1-((2S)-2-methyl-4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (7.45 g, 11.47 mmol, 84% yield) as an off-white foam. m/z (ESI, +ve) 650.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.41-8.47 (m, 1H); 8.21-8.25 (m, 1H); 7.20-7.25 (m, 4H); 6.83-6.89 (m, 4H); 4.81 (d, J=8.61 Hz, 4H); 4.02 (q, J=6.78 Hz, 1H); 3.81 (s, 3H); 3.79 (s, 3H); 3.28-3.35 (m, 1H); 3.12-3.20 (m, 1H); 3.05-3.10 (m, 1H); 2.92-2.99 (m, 1H); 2.87 (ddd, J=11.44, 7.92, 3.33 Hz, 1H); 2.70 (s, 3H) 2.60-2.68 (m, 2H) 2.55 (s, 3H) 1.43 (d, J=6.85 Hz, 3H) 1.08 (d, J=6.46 Hz, 3H).