Reaction SMILES: [CH3:1][O:2][C:3]1[CH:45]=[CH:44][C:6]([CH2:7][N:8]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([CH:32](O)[CH3:33])[CH:19]=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=3)[N:10]=2)=[CH:5][CH:4]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:58][S:59]([N:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1)(=[O:61])=[O:60]>C(Cl)Cl.O>[F:29][C:27]1[CH:28]=[C:23]([NH:22][C:21]2[C:16]([C:11]3[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([N:8]([CH2:7][C:6]4[CH:44]=[CH:45][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[CH2:35][C:36]4[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=4)[N:10]=3)=[CH:17][C:18]([CH:32]([N:65]3[CH2:66][CH2:67][N:62]([S:59]([CH3:58])(=[O:61])=[O:60])[CH2:63][CH2:64]3)[CH3:33])=[CH:19][N:20]=2)[CH:24]=[N:25][C:26]=1[O:30][CH3:31]
Reactant: CS(=O)(=O)N1CCNCC1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(C(C)O)cnc3Nc3cnc(OC)c(F)c3)n2)cc1
Agent: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(C(C)N4CCN(S(C)(=O)=O)CC4)cnc3Nc3cnc(OC)c(F)c3)n2)cc1
Reaction time: 0.33 h
Yield: 42.5 %

Procedure:
1-(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanol (867.1 mg, 1.418 mmol) was dissolved in DCM (22 mL) and the flask was cooled in an ice water bath. Then, triethylamine (0.90 mL, 6.5 mmol) and methanesulfonyl chloride (0.41 mL, 5.3 mmol) were added, and the reaction was stirred under nitrogen. After 20 min, the reaction was diluted with DCM (125 mL) and treated with water (25 mL). The layers were separated, and the aqueous phase was extracted with DCM. The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and dissolved in DCM (15 mL). Triethylamine (0.90 mL, 6.5 mmol) and 1-methanesulfonylpiperazine (753.9 mg, 4.591 mmol) were added and the reaction was stirred under nitrogen at room temperature overnight. Then, the reaction was treated with water (20 mL) and diluted with DCM. The layers were separated, and the aqueous phase was extracted with DCM. The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (150 mL fritted filter with about 2 inches of silica gel; DCM to 50:1 DCM/MeOH to 30:1 DCM/2N ammonia in MeOH to 15:1 DCM/2 N ammonia in MeOH to 10:1 DCM/2N ammonia in MeOH). The product eluted with 50:1 DCM/MeOH. The fractions with product were collected, concentrated, and repurified on a silica gel filter (150 mL fritted filter with about 2 inches of silica gel; 100:1 DCM/MeOH, to elute impurities to 40:1 DCM/MeOH, to elute product) to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (456.7 mg). 1H NMR (CDCl3, 400 MHz) δ 11.87 (s, 1H), 8.72 (d, J=2.35 Hz, 1H), 8.25 (d, J=2.35 Hz, 1H), 8.07 (d, J=12.32 Hz, 2.15 Hz, 1H), 7.97 (d, J=2.35 Hz, 1H), 7.22 (t, J=8.51 Hz, 4H), 6.91-6.82 (m, 4H), 4.93-4.76 (m, 4H), 4.02 (s, 3H), 3.82 (s, 3H), 3.79 (s, 3H), 3.55 (q, J=6.78 Hz, 1H), 3.16 (t, J=4.60 Hz, 4H), 2.69 (s, 3H), 2.60 (s, 3H), 2.58-2.49 (m, 4H), 1.38 (d, J=6.65 Hz, 3H). m/z (ESI, pos. ion) 758 (M+H)+.