Reaction SMILES: [Li+].CCC[CH2-].C(NC(C)C)(C)C.[C:13]([C:17]1[CH:22]=[C:21]([CH3:23])[N:20]=[CH:19][N:18]=1)([CH3:16])([CH3:15])[CH3:14].[Br:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[N:31]=[C:30]([NH:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:29]([CH:40]=[O:41])=[CH:28]2>C1COCC1>[Br:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[N:31]=[C:30]([NH:35][C:36]([CH3:37])([CH3:39])[CH3:38])[C:29]([CH:40]([OH:41])[CH2:23][C:21]1[CH:22]=[C:17]([C:13]([CH3:16])([CH3:15])[CH3:14])[N:18]=[CH:19][N:20]=1)=[CH:28]2
Reactant: Cc1cc(C(C)(C)C)ncn1
Reactant: CC(C)(C)Nc1nc2ccc(Br)cc2cc1C=O
Agent: [CH2-]CCC
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CC(C)(C)Nc1nc2ccc(Br)cc2cc1C(O)Cc1cc(C(C)(C)C)ncn1
Temperature: -78 °C
Reaction time: 1.5 h

Procedure:
Cyanocopper (1.9 g, 21.5 mmol) and lithium chloride (1.8 g, 42.9 mmol) were stirred in THF (30 mL) until dissolved (approximately 20 min) and then cooled to 0° C. Next, tert-butyllithium (12.6 mL, 21.5 mmol) was slowly added the resulting solution was stirred at 0° C. for 25 min before cooling to −78° C. 4-Chloro-6-methylpyrimidine (2.3 g, 17.9 mmol) in THF (5 mL) was added and the reaction was allowed to warm to RT over 12 h. The reaction mixture was diluted with 10:1 saturated NH4Cl/NH4OH and extracted with EtOAc. The combined organic extracts were washed with 10:1 saturated NH4C1/NH4OH, water, brine, and dried over Na2SO4. The solution was filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography by eluting with 1:4 EtOAc in hexane to provide 4-tert-butyl-6-methylpyrimidine. Step 2: A solution of N-butyllithium solution, 2.5M in hexanes (5.2 mL, 13.0 mmol) was added to a solution of diisopropylamine (2.2 mL, 15.6 mmol) in THF (15 mL) cooled to −78° C. After the addition, the solution was warmed to 0° C. for 15 min before cooling again to −78° C. Then 4-tert-butyl-6-methylpyrimidine (2.0 g, 13.0 mmol) in THF (4 mL) was slowly added and then the reaction was stirred for 1.5 h at −78° C. 6-bromo-2-(tert-butylamino)quinoline-3-carbaldehyde (2.0 g, 6.51 mmol) in THF (6 mL) was then added via syringe and stirred 15 min before quenching with saturated NH4Cl. The reaction was diluted reaction with EtOAc and the layers were separated. The aqueous layer was extracted with ethyl acetate and brine, and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material. Purification by silica gel chromatography (2:1 Hex/EtOAc) afforded 1-(6-bromo-2-(tert-butylamino)quinolin-3-yl)-2-(6-tert-butylpyrimidin-4-yl)ethanol. Step 3: Trifluoroacetic anhydride (1.5 mL, 2.0 mmol) was added to a solution of 1-(6-bromo-2-(tert-butylamino)quinolin-3-yl)-2-(6-tert-butylpyrimidin-4-yl)ethanol (0.46 g, 1.0 mmol) in Pyridine (6 mL) at 0° C. The reaction mixture was allowed to warm to RT and then heated at 50° C. for 6 h. The reaction was concentrated and dissolved in a minimal amount of DCM and purified by passing through a plug of silica gel and eluting with 10:1 Hex/EtOAc to afford (E)-6-bromo-N-tert-butyl-3-(2-(6-tert-butylpyrimidin-4-yl)vinyl)quinolin-2-amine. Step 4: A-Phos (0.054 g, 0.076 mmol) and potassium acetate (0.30 g, 3.1 mmol) were added to (E)-6-bromo-N-tert-butyl-3-(2-(6-tert-butylpyrimidin-4-yl)vinyl)quinolin-2-amine (0.67 g, 1.53 mmol) in degassed (N2) solution of ethanol (12 mL)/water (2 mL). The reaction was evacuated and flushed with N2 gas three times before being refluxed. After 12 h the reaction was allowed to cool and was diluted with 10:1 saturated NR1Cl/NR4OH and extracted with CH2Cl2. The combined organic extracts were washed with 10:1 saturated NH4Cl/NH4OH, water, brine, and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material. The crude material was purified by silica gel chromatography by eluting with 1:2 EtOAc in hexane to provide (E)-N-tert-butyl-3-(2-(6-tert-butylpyrimidin-4-yl)vinyl)-6-o-tolylquinolin-2-amine. Step 5: (E)-N-tert-butyl-3-(2-(6-tert-butylpyrimidin-4-yl)vinyl)-6-o-tolylquinolin-2-amine (0.10 g, 0.22 mmol) was stirred in TFA (1.0 mL, 13.0 mmol) for 3.5 h and concentrated. The crude material was dissolved in CH2Cl2 and washed with saturated NaHCO3. The aqueous layers were back extracted with CH2Cl2 and the combined organic extracts were washed with saturated NaCl, and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material taken directly for the next reaction. The crude material was dissolved in ethanol (2.0 mL) and was degassed with nitrogen. 10% Pd/C (0.024 g, 0.22 mmol) was added and the resulting mixture is degassed briefly with nitrogen and then degassed with hydrogen through a balloon. The reaction was stirred 3 h under a balloon of hydrogen and then degassed with nitrogen and filtered through celite with ethyl acetate. The crude product was purified by silica gel chromatography (20:1 Dichlormethane/MeOH 2M NH3) to provide 3-(2-(6-tert-butylpyrimidin-4-yl)ethyl)-6-o-tolylquinolin-2-amine. (ESI, pos. ion) m/z: 397 (M+1).