Reaction SMILES: C[O:2][C:3]([C:5]1([C:8]2[CH:45]=[CH:44][CH:43]=[CH:42][C:9]=2[CH2:10][CH2:11][C:12]2[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]3[CH:24]=[CH:25][C:26]([CH:29]4[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]4)=[N:27][CH:28]=3)[N:13]=2)[CH2:7][CH2:6]1)=O.O[Li].O.C1C=CC2N(O)N=[N:55]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.C(NC(C)C)(C)C.C(=O)([O-])[O-].[NH4+].[NH4+]>C1COCC1.CO.O>[C:3]([C:5]1([C:8]2[CH:45]=[CH:44][CH:43]=[CH:42][C:9]=2[CH2:10][CH2:11][C:12]2[C:17]([C:18]([F:19])([F:20])[F:21])=[CH:16][N:15]=[C:14]([NH:22][C:23]3[CH:24]=[CH:25][C:26]([CH:29]4[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:39])[CH3:40])=[O:36])[CH2:31][CH2:30]4)=[N:27][CH:28]=3)[N:13]=2)[CH2:6][CH2:7]1)(=[O:2])[NH2:55]
Reactant: COC(=O)C1(c2ccccc2CCc2nc(Nc3ccc(C4CCN(C(=O)OC(C)(C)C)CC4)nc3)ncc2C(F)(F)F)CC1
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(Nc3ncc(C(F)(F)F)c(CCc4ccccc4C4(C(N)=O)CC4)n3)cn2)CC1
Temperature: 40 °C
Reaction time: 16 h

Procedure:
A solution of tert-butyl 4-(5-((4-(2-(1-(methoxycarbonyl)cyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate (A11) (112 mg, 0.179 mmol) and LiOH.H2O (90 mg, 2.2 mmol) in THF (7.0 mL), MeOH (7.0 mL) and H2O (2.0 mL) was stirred at 35° C. for 24 hours. Additional LiOH.H2O (45 mg, 1.1 mmol) was added and stirring continued at 35° C. for 16 hours. Further LiOH.H2O (45 mg, 1.07 mmol) was added and stirring was continued at 35° C. for 3 days. The volatiles were removed in vacuo and the residue diluted with EtOAc (20 mL) and aqueous HCl (2 M, 20 mL). The layers were separated and the aqueous phase was extracted with EtOAc (2×50 mL). The combined organics extracts were washed with brine and dried over MgSO4. The volatiles were removed in vacuo and the residue dissolved in anhydrous THF (9.0 mL) and anhydrous DMF (1.5 mL) then HOBt (48 mg, 0.36 mmol), EDCl.HCl (68 mg, 0.36 mmol) and diisopropylamine (0.310 mL, 2.21 mmol) were added under an atmosphere of nitrogen. After 10 minutes of stirring ammonium carbonate (86 mg, 0.89 mmol) was added in one portion and the resulting mixture was stirred at room temperature for 16 hours. The temperature was raised to 40° C. and stirring was continued for a further 24 hours. The volatiles were removed in vacuo before EtOAc (20 mL) and saturated NaHCO3 (20 mL) were added to the residue. After separating the layers, the aqueous phase was extracted with EtOAc (2×20 mL) then the combined organic extracts were washed with brine and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by silica gel column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 10-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A12 as a white solid (77 mg, 71%); 1H NMR (400 MHz, d6-DMSO) δ 10.32 (s, 1H), 8.76 (d, J=2.5 Hz, 1H), 8.72 (s, 1H), 8.14 (d, J=6.7 Hz, 1H), 7.37-7.26 (m, 4H), 7.26-7.18 (m, 1H), 6.98 (s, 1H), 6.02 (s, 1H), 4.05 (d, J=12.7 Hz, 2H), 3.21-3.07 (m, 4H), 2.87-2.75 (m, 3H), 1.81 (d, J=11.1 Hz, 2H), 1.56 (qd, J=13.0, 4.4 Hz, 2H), 1.47-1.38 (m, 11H), 0.97 (s, 2H). LCMS-A: rt 5.273 min; m/z 611 [M+H]+.