Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](N(OC)C)=[O:13])=[CH:5]2.[CH3:18][Mg]Br>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:13])[CH3:18])=[CH:5]2
Reactant: CON(C)C(=O)c1cnc2ccc(Br)cc2c1
Reactant: C[Mg]Br
Solvent: C1CCOC1
Product: CC(=O)c1cnc2ccc(Br)cc2c1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
To a 500 mL RBF containing 6-bromoquinoline-3-carboxylic acid (1.0 g, 4.0 mmol) was added THF (15 mL) and the mixture was allowed to stir at 23° C. for 2 min. At this time, 4-methylmorpholine (1.3 ml, 12 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (1.0 g, 6.0 mmol) were added in single portions. The reaction was allowed to stir for 1 h and then N,O-dimethylhydroxylamine HCl (0.43 g, 4.4 mmol) was added in one portion. The reaction was allowed to stir overnight and the diluted with water. It was extracted with EtOAc (3×). The combined organics were washed with sodium carbonate (3× 10%), ammonium chloride (2× sat.), sodium bicarbonate and brine. It was dried with magnesium sulfate, filtered and concentrated to give an off white solid. The reaction was repeated on a 3.0 g scale of 6-bromoquinoline-3-carboxylic acid. The combined yield material was purified by column chromatography on a 120 g Isco column (eluting with 30 to 60% EtOAc in hexanes) to give 6-bromo-N-methoxy-N-methylquinoline-3-carboxamide Step 2 To a 500 mL RBF containing 6-bromo-N-methoxy-N-methylquinoline-3-carboxamide (4.00 g, 13.6 mmol) was added THF (50 mL) and the mixture was allowed to stir at 0° C. for 5 min. At this time, methyl magnesium bromide (3 M in ether) (4.5 mL, 13.6 mmol) was added in a fast dropwise manner. After 1 h the material was quenched with the addition sodium bicarbonate (sat 100 mL) and extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried with sodium sulfate, filtered, concentrated and subjected to 80 g Isco column to give 1-(6-bromoquinolin-3-yl)ethanone as a white solid. Step 3 1-(6-bromoquinolin-3-yl)ethanone (170 mg, 680 μmol) was placed in a microwave tube and toluene (2 mL) was added before the addition of methyl(triphenylphosphoranylidene)acetate (227 mg, 680 μmol) in one portion. The tube was irradiated in the microwave at 140° C. for 10 min. An additional portion of (triphenylphosphoranylidene)acetate (80 mg) was added to the tube and it was then irradiated in the microwave at 160° C. for 60 min. The crude reaction material was loaded directly to a 40 g Isco column and purified to give methyl 3-(6-bromoquinolin-3-yl)but-2-enoate (representative compound 23) as a mixture of E and Z isomers. Step 4 A microwave tube (25 mL) was charged with 1,4-dioxane (4 mL) and methyl 3-(6-bromoquinolin-3-yl)but-2-enoate (320 mg, 1045 μmol). O-tolylboronic acid (242 mg, 1777 μmol) was added to the tube followed by sodium carbonate (1045 μl, 2090 μmol) and tetrakis(triphenylphosphine)palladium(0) (60 mg). The tube was irradiated in a microwave at 90° C. for 20 min. The crude mixture was diluted with sodium bicarbonate (75 mL, sat) and extracted with EtOAc (3×30 mL). The combined organics were washed with brine, dried with sodium sulfate, filtered and concentrated to give methyl 3-(6-o-tolylquinolin-3-yl)but-2-enoate (representative compound 24) as a yellow oil. The material was taken directly to the next reaction. Step 5 To a 500 mL RBF containing methyl 3-(6-o-tolylquinolin-3-yl)but-2-enoate (325 mg, 1024 μmol) was added THF (6 mL) and water (2 mL) the mixture was allowed to stir at 23° C. for 2 min. At this time, LiOH (245 mg, 10240 μmol) and the reaction was allowed to stir for 48 h. The material was poured into EtOAc (50 mL) and HCl (0.5 M, 100 mL) was added to the flask. The layers were separated and the aqueous layer was extracted with dichloromethane (4×30 ml). The combined organic layers were washed with brine, dried with sodium sulfate, filtered and concentrated to give carboxylic acid (369 mg). The crude acid was dissolved in NMP (4928 μL, 51200 μmol) and DIPEA (715 μL, 4096 μmol) was added before the addition of cyclohexanemethylamine (348 μL, 3072 μmol) and tbtu coupling reagent (493 mg, 1536 μmol). The reaction was allowed to stir for 12 h and then poured into sodium bicarbonate. The aqueous layer was extracted with EtOAc (3×25 mL). The combined organics were washed the brine, dried with sodium sulfate, filtered and purified on a 40 g Isco chromatography column to give (N-(cyclohexylmethyl)-3-(6-o-tolylquinolin-3-yl)but-2-enamide (representative compound 25). Step 6 A RBF (25 mL) was charged with (cyclohexylmethyl)-3-(6-o-tolylquinolin-3-yl)but-2-enamide (184 mg), MeOH (15 mL) and palladium on carbon (10% by weight, 50 mg). Hydrogen gas was bubbled through the reaction for 15 min and then it was allowed to stir for 2 h under 1.0 atm of hydrogen. The crude mixture was passed though a plug of silica gel under a pad of celite and eluted with EtOAc. The volatiles were removed by rotary evaporation to give N-(cyclohexylmethyl)-3-(6-o-tolylquinolin-3-yl)butanamide (representative compound 26). The material was used directly in the next reaction with no further purification. Step 7 To a RBF (50 mL) containing N-(cyclohexylmethyl)-3-(6-o-tolylquinolin-3-yl)butanamide (185 mg) was added DCM (15 mL) and the flask was placed on an ice bath. After 10 min, mCPBA (239 mg, 3 eq) was added in one portion, and the reaction was allowed to stir for 30 min and then diluted with DCM (75 mL). The organic layer was washed with sodium bicarbonate (sat, 3×50 mL), brine and dried with sodium sulfate. The dried solution was filtered, concentrated and diluted with 1-(trifluoromethyl)benzene (10 mL). To the RBF containing the N-oxide was added tert-butylamine (338 mg, 10 eq) followed by p-toluenesulfonic anhydride (196 mg, 1.3 eq) portion wise over 3 min. After 5 min, the crude reaction was diluted with DCM (50 ml), washed with NaOH (1N, 2×50 mL), sodium bicarbonate (sat, 1×50 mL), brine, dried with sodium sulfate. The dried solution was filtered and concentrated to give 300 mg crude brown oil. This material was chromatographed on a 40 g Isco column (5 to 35% EtOAc in hexanes) to give 3-(2-(tert-butylamino)-6-o-tolylquinolin-3-yl)-N-(cyclohexylmethyl)butanamide. A portion of this material was treated with TFA (5 mL) at 72° C. for 1 h. The TFA was removed by rotary evaporator and the residue diluted with DCM. The organic layer was washed with NaOH (1N, 50 mL). The aqueous layer was back extracted with DCM, washed with brine, dried with sodium sulfate, filtered and concentrated to give 3-(2-amino-6-o-tolylquinolin-3-yl)-N-(cyclohexylmethyl)butanamide (representative compound 27) of a slightly brown oil. MS (ESI, pos. ion) m/z: 412 (M+1).