Reaction SMILES: [CH:1]1[N:5]=[CH:4][N:3]([C:6]([N:8]2C=NC=C2)=[O:7])[CH:2]=1.NC(C(C)(C)C)C(C1C=CC(C#N)=CC=1)=O.Cl>CN(C=O)C>[NH2:3][C:6]([NH2:8])=[O:7].[NH:3]1[CH:2]=[CH:1][N:5]=[CH:4]1
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: CC(C)(C)C(N)C(=O)c1ccc(C#N)cc1
Agent: Cl
Solvent: CN(C)C=O
Product: NC(N)=O
Product: c1c[nH]cn1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a cleaned and dried 10 L reactor at Tj 22° C. was added CDI (153.7 g; 0.74 mol; 1.5 eq) followed by DMF (1 L; 8.0 vol) giving a clear pale yellow solution. To the solution above was added at Tj 22° C., 10 portions of a pre-made suspension/solution of 4-(2-amino-3,3-dimethylbutanoyl)benzonitrile×HCl (Example 3 prepared by method 2; 135 g; 0.50 mol; 1.0 eq), DMF (1 L; 8.0 vol) and TEA (127 g; 1.26 mol) during 30 min. The temperature was increased to 25° C. and the resulting mixture was stirred for 30 min. An IPC was taken (GC) to give full conversion of starting material to imidazole urea intermediate. Tj was set to 5° C. and TEA (247.5 g; 5 eq) was added to the reaction mixture <10° C. To the mixture was added during 33 min portion-wise 1-(6-methylpyridin-2-yl)piperazine×2HCl (Example 4; 184 g; 1.50 eq) maintaining the inner temperature <30° C. The reaction mixture was stirred for another 30 min at Tj 25° C. and an IPC was taken giving a conversion of 99.5% (HPLC). The mixture was cooled (Tj 5° C.) and left overnight. To the mixture at 5° C. was added in portions an aq solution of NH4Cl (285 g; 10 eq) in water (2.0 L; 15 vol) during 8 min. The Tj was set to 25° C. and to the resulting mixture was added toluene (2.26 L; 16.7 vol). The organic phase was recovered and the water phase was extracted once with toluene (2.26 L; 16.7 vol). The organic phases were combined, washed with water (500 mL; 3.7 vol) and extracted twice with a solution of 2× HCl (30% w/w; 127 mL; 2 eq) in water (2.5 L; 18.5 vol). The acid water phase was washed with toluene (1.1 L; 8.1 vol). The organic layer was recovered and the water phase was recharged to the reactor and EtOAc (2.3 L; 17 vol) was added. To the mixture at 25° C. was added a pre-made aq solution of NaHCO3 (249 g; 5.9 eq) in water (pH 8) under stirring. The basic aq phase was recovered, washed with EtOAc (2.2 L; 16 vol), organic phases were combined and washed with brine (400 mL) and the solution left overnight at Tj 15° C. The organic layer (4 L) was concentrated in vacuo at 40° C. to approx half volume, mixed with SiO2 (approx 250 g) and the solvent was removed to give a silica powder column head. The silica column head was placed on a pre-packed silica column with EtOAc (120 mm×400 mm; approx 4 kg SiO2 40-60 mesh). The flash chromatography procedure used approx 20 L EtOAc as eluent and the process was monitored by TLC. Fractions (approx 250 mL) were pooled after TLC analyses and concentrated in vacuo at 40° C. The obtained product was dried in vacuo at 40° C. to give 191.5 g of pure white material. Analyses gave a HPLC purity of 99.7 area-% (254 nm) and an assay of 98.5% w/w. Residual solvent EtOAc 0.1% w/w. This material (180 g) was used for preparation of the desired enantiomer, N-(1-(4-cyanophenyl)-3,3-dimethyl-1-oxobutan-2-yl)-4-(6-methylpyridin-2-yl)piperazine-1-carboxamide. Yield 90% based on NMR assay (calculated).