Reaction SMILES: C([Li])CCC.[CH3:6][C:7]1[CH:16]=[CH:15][C:14]([CH2:17][N:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)=[CH:13][C:8]=1[C:9]([NH:11][CH3:12])=O.[Si]([O:32][C:33]1[C:40]([CH3:41])=[CH:39][C:36]([C:37]#[N:38])=[CH:35][C:34]=1[CH3:42])(C(C)(C)C)(C)C>C1COCC1>[CH3:41][C:40]1[CH:39]=[C:36]([C:37]2[N:38]=[C:9]([NH:11][CH3:12])[C:8]3[C:7]([CH:6]=2)=[CH:16][CH:15]=[C:14]([CH2:17][N:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)[CH:13]=3)[CH:35]=[C:34]([CH3:42])[C:33]=1[OH:32]
Reactant: CNC(=O)c1cc(CN2CCN(C)CC2)ccc1C
Reactant: Cc1cc(C#N)cc(C)c1O[Si](C)(C)C(C)(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CNc1nc(-c2cc(C)c(O)c(C)c2)cc2ccc(CN3CCN(C)CC3)cc12
Temperature: -50 °C
Reaction time: 1 h
Yield: 37.4 %

Procedure:
To a solution of 5-bromomethyl-2,N-dimethylbenzamide (4.94 g, 24 mmol) in anhydrous THF (75 mL) was added N-methylpiperazine (5.3 mL, 4.81 g, 48 mmol). A white precipitate was formed. Stirring continued overnight. Water (100 mL) was added, and the mixture was extracted with ethyl acetate (200 mL). The organic layer was washed with brine and dried over anhydrous Na2SO4. Purification by column chromatography (Silica Gel 230-400 mesh; 0-5% methanol (containing 7.0 M ammonia) in CH2Cl2 as eluent) to give 2,N-dimethyl-5-(4-methylpiperazin-1-ylmethyl)benzamide (2.4 g, 38%) of as a gummy material. n-Butyl lithium (9.1 mL, 14.64 mmol, 1.6 M solution in hexanes) was added to a solution of 2,N-dimethyl-5-(4-methylpiperazin-1-ylmethyl)benzamide (0.87 g, 3.33 mmol) in anhydrous THF (10 mL) dropwise at −10° C. over a period of 10 min under nitrogen. Color changed to orange-red. Stirring continued at 0° C. for 1 hour. The reaction mixture was cooled to −50° C. A solution of 4-(tert-butyldimethylsilanyloxy)-3,5-dimethylbenzonitrile (1.09 g, 4.16 mmol) in anhydrous THF (5 mL) was quickly added. Cooling bath was removed and the reaction mixture was allowed to warm to room temperature. Stirring was continued at room temperature for 1 hour. The reaction mixture became dark colored. An aqueous ammonium chloride solution (20 mL) was added. The color changed to pale yellow. Ethyl acetate (50 mL) was added. The organic layer was separated, washed with water (10 mL) and dried (Na2SO4). Removal of the solvent gave a yellow gummy material, which was used in next step without further purification. The above compound (1.87 g) was dissolved in anhydrous THF (10 mL). Tetrabutyl ammonium fluoride (6.8 mL, 1.0M solution in THF) was added at 0° C. The reaction mixture was stirred at 0° C. for 30 min. and then at room temperature for 1 hour. Saturated aqueous ammonium chloride (30 mL) was added. The mixture was extracted with ethyl acetate (100 mL) and the organic layer was separated and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, the crude product was purified by column chromatography (Silica Gel 230-400 mesh; 0-5% methanol (containing 7.0 M ammonia) in CH2Cl2 as eluent) to give 2,6-dimethyl-4-[1-methylamino-7-(4-methylpiperazin-1-ylmethyl) isoquinolin-3-yl]phenol (0.487 g, 33%) as purple solid. To a solution of above compound (0.17 g, 0.43 mmol) in CH2Cl2 (10 mL) was added hydrogen chloride in ether (2.0 mL, 1.0 M solution) dropwise under nitrogen. A yellow precipitate was formed. The reaction mixture was stirred at room temperature for 11 hour. Solvent was removed under reduced pressure and dried under vacuum to give 2,6-dimethyl-4-(1-(methylamino)-7-((4-methylpiperazin-1-yl)methyl)isoquinolin-3-yl)phenol (0.178 g, 97%) as the trihydrochloride; MS (ES) m/z: 391.10 (M+1); MP 264-266° C.