Reaction SMILES: CS(O[CH:6]([C:8]1[CH:9]=[N:10][C:11]([NH:40][C:41]2[CH:42]=[N:43][C:44]([O:48][CH3:49])=[C:45]([F:47])[CH:46]=2)=[C:12]([C:14]2[N:19]=[C:18]([N:20]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)[CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[N:17]=[C:16]([CH3:39])[N:15]=2)[CH:13]=1)[CH3:7])(=O)=O.CC#N.CC1(C)CCCC(C)(C)N1.[CH3:63][C@@H:64]1[NH:69][CH2:68][CH2:67][N:66]([C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])[CH2:65]1>O.C(Cl)Cl>[CH3:29][O:28][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][N:20]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=2)[C:18]2[N:17]=[C:16]([CH3:39])[N:15]=[C:14]([C:12]3[CH:13]=[C:8]([C@@H:6]([N:69]4[CH2:68][CH2:67][N:66]([C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])[CH2:65][C@@H:64]4[CH3:63])[CH3:7])[CH:9]=[N:10][C:11]=3[NH:40][C:41]3[CH:42]=[N:43][C:44]([O:48][CH3:49])=[C:45]([F:47])[CH:46]=3)[N:19]=2)=[CH:27][CH:26]=1.[CH3:29][O:28][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][N:20]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=2)[C:18]2[N:17]=[C:16]([CH3:39])[N:15]=[C:14]([C:12]3[CH:13]=[C:8]([C@H:6]([N:69]4[CH2:68][CH2:67][N:66]([C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])[CH2:65][C@@H:64]4[CH3:63])[CH3:7])[CH:9]=[N:10][C:11]=3[NH:40][C:41]3[CH:42]=[N:43][C:44]([O:48][CH3:49])=[C:45]([F:47])[CH:46]=3)[N:19]=2)=[CH:27][CH:26]=1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(C(C)OS(C)(=O)=O)cnc3Nc3cnc(OC)c(F)c3)n2)cc1
Reactant: C[C@H]1CN(C(=O)OC(C)(C)C)CCN1
Agent: CC1(C)CCCC(C)(C)N1
Solvent: ClCCl
Solvent: O
Solvent: CC#N
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc([C@@H](C)N4CCN(C(=O)OC(C)(C)C)C[C@@H]4C)cnc3Nc3cnc(OC)c(F)c3)n2)cc1
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc([C@H](C)N4CCN(C(=O)OC(C)(C)C)C[C@@H]4C)cnc3Nc3cnc(OC)c(F)c3)n2)cc1
Temperature: 25 °C
Yield: 17.8 %
Yield: 17.8 %

Procedure:
A stirred solution of crude 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)ethyl methanesulfonate (0.492 g, 0.713 mmol) in CH3CN (10.00 mL, 191 mmol) was treated with 2,2,6,6-tetramethylpiperidine (0.182 mL, 1.070 mmol) and (S)-tert-butyl 3-methylpiperazine-1-carboxylate (Aldrich, St. Louis, Mo., 0.186 g, 0.927 mmol) and the mixture was heated at reflux overnight. The mixture was then allowed to cool to room temperature, and the resulting suspension was diluted with water and DCM (20 mL each). The organic layer was separated, and the aqueous layer was extracted with DCM (2×20 mL). All organic layers were then combined, washed with brine, dried over Na2SO4, and concentrated. The residue was purified by flash column chromatography (silica gel, 0% to 15% ethyl acetate/DCM, followed elution with 5% MeOH/DCM) to give the two separated diasteromers (S)-tert-butyl 4-((S)-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)ethyl)-3-methylpiperazine-1-carboxylate (first eluting diastereomer; 101 mg, 17.8%) and (S)-tert-butyl 4-((R)-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)ethyl)-3-methylpiperazine-1-carboxylate (second eluting diastereomer; 101 mg, 17.8%). Absolute stereochemistries of the two diastereomers were determined by co-crystal structure of Example 272 (derived from the second eluting distereomer) in complex with PI3Kγ at 2.9 Å resolution. m/z (ESI, +ve ion) 794 (M+H)+.