Reaction SMILES: Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][C:14]=2[O:28][CH3:29])[N:3]=1.[NH2:30][C:31]1[CH:32]=[CH:33][C:34]([CH:42]2[CH2:47][CH2:46][C:45]([O:52][Si](C(C)(C)C)(C)C)([C:48]([O:50]C)=[O:49])[CH2:44][CH2:43]2)=[C:35]2[C:39]=1[C:38](=[O:40])[N:37]([CH3:41])[CH2:36]2.C(O)(C(F)(F)F)=O.CCCC[N+](CCCC)(CCCC)CCCC.[F-].O.[OH-].[Li+].Cl>CCOC(C)=O.C1COCC1.O.CO>[CH2:20]([O:19][P:18]([CH2:17][C:16]1[CH:26]=[CH:27][C:13]([NH:12][C:4]2[N:3]=[C:2]([NH:30][C:31]3[CH:32]=[CH:33][C:34]([CH:42]4[CH2:43][CH2:44][C:45]([OH:52])([C:48]([OH:50])=[O:49])[CH2:46][CH2:47]4)=[C:35]4[C:39]=3[C:38](=[O:40])[N:37]([CH3:41])[CH2:36]4)[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=2)=[C:14]([O:28][CH3:29])[CH:15]=1)([O:22][CH2:23][CH3:24])=[O:25])[CH3:21]
Reactant: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Cl)n2)c(OC)c1)OCC
Reactant: COC(=O)C1(O[Si](C)(C)C(C)(C)C)CCC(c2ccc(N)c3c2CN(C)C3=O)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: Cl
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O=C(O)C(F)(F)F
Product: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(C4CCC(O)(C(=O)O)CC4)c4c3C(=O)N(C)C4)n2)c(OC)c1)OCC
Temperature: 25 °C
Reaction time: 8 h
Yield: 36 %

Procedure:
A solution of diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (105 mg, 0.23 mmol) and methyl 4-(7-amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)-1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexanecarboxylate (Compound 278A, 110 mg, 0.26 mmol) in TFE (3 mL) was charged with TFA (75 mg, 0.66 mmol) and irradiated on the microwave at 100° C. for 30 min. The reaction mixture was diluted with EtOAc (30 mL), washed with sat. aq. NaHCO3 (2×10 mL), brine (10 mL), and dried over anhydrous sodium sulfate. The solvents were evaporated under reduced pressure, and the crude material was used in next step without further purification. The above material was dissolved in THF (6 mL), then TBAF (2.0 mL, 2.0 mmol, 1M solution in THF) was added. The resulting mixture was stirred at rt overnight. The reaction mixture was diluted with EtOAc (30 mL), washed with water (10 mL), brine (10 mL), and dried over anhydrous sodium sulfate. The solvents were evaporated under reduced pressure, and the crude material was used in the hydrolysis without further purification. The above crude ester was dissolved in THF (2 mL), MeOH (2 mL) and H2O (2 mL), then lithium hydroxide monohydrate (48.5 mg, 1.16 mmol) was added. The resulting mixture was stirred at rt for 1 h. The mixture was acidified with aq. 1M HCl to pH=3, then extracted with EtOAc (3×10 mL), the combined organic phases were washed with brine (10 mL), and dried over anhydrous sodium sulfate. The solvents were evaporated under reduced pressure and the residue was purified by silica gel chromatography (ISCO system: MeOH/DCM=0-10%) to give the title compound as a white solid, 62 mg, 36% yield over three steps. LC-MS and 1H NMR showed that it was a single isomer. 1H NMR (DMSO-d6): 1.20 (t, J=7.0 Hz, 6H), 1.55-1.65 (m, 2H), 1.74-1.99 (m, 6H), 2.58 (m, 1H), 3.07 (s, 3H), 3.24 (d, J=21.2 Hz, 2H), 3.76 (s, 3H), 3.95-4.04 (m, 4H), 4.51 (s, 2H), 4.99 (s, 1H), 6.90 (d, J=7.8 Hz, 1H), 7.05 (s, 1H), 7.26 (m, 1H), 7.51 (m, 1H), 8.38 (s, 1H), 8.98 (s, 1H), 10.57 (s, 1H), 12.38 (s, 1H). MS (ES+): m/z=722.17 [MH+]. HPLC: tR=3.43 min (ZQ3, polar—5 min).