[1-(4-Bromo-phenyl)-1-methyl-ethyl]-carbamic acid tert-butyl ester

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2-(4-bromophenyl)-2-methylpropanamide (3 g) in tert-butanol (31 mL) was added [bis(trifluoroacetoxy)iodo]benzene (8 g) portionwise at room temperature. The reaction mixture was stirred at reflux temperature for 30 min Pyridine (3 mL) was added to the mixture. After being stirred at reflux temperature for 1 h, the reaction mixture was concentrated to dryness. The residue was dissolved in benzene and washed with 1 M citric acid aqueous solution (2 times), sodium bicarbonate aqueous solution (5 times) then brine. The organics were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (0-20% ethyl acetate in hexanes) gave the product (3.29 g, 84%). 1HNMR (CDCl3) 400 MHz δ: 7.43 (d, J=8.6 Hz, 2H), 7.27 (d, J=8.6 Hz, 2H), 1.59 (br s, 6H), 1.48-1.05 (m, 9H). was added to the mixture After being stirred at reflux temperature for 1 h the reaction mixture was concentrated to dryness The residue was dissolved in benzene washed with 1 M citric acid aqueous solution (2 times), sodium bicarbonate aqueous solution (5 times) The organics were dried over anhydrous sodium sulfate concentrated under reduced pressure Purification by column chromatography (0-20% ethyl acetate in hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following General Procedure E, tert-butyl 2-(4-bromophenyl)propan-2-ylcarbamate (0.44 g, 1.4 mmol) was reacted with 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (0.45 g, 1.4 mmol) to afford the desired product (0.53 g, 79%) as a brown solid: ESI MS m/z 479 [C27H30N2O4S+H]+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following General Procedure E, tert-butyl 2-(4-bromophenyl)propan-2-ylcarbamate (160 mg, 0.50 mmol) was reacted with bis(pinacolato)diboron (140 mg, 0.55 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (140 mg, 0.45 mmol) to afford the desired product (110 mg, 47%) as a brown solid: ESI MS m/z 465 [C26H28N2O4S+H]+. to afford the crude boronic ester which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4-bromophenyl)propan-2-amine, hydrochloric acid (1.0 g, 4.0 mmol, AKOS) in DCM (30 mL) at about 0° C. was added TEA (1.11 mL, 7.98 mmol). A solution of BOC2O (1.623 ml, 7.01 mmol) in DCM (10 mL) was added dropwise over about 10 min. After about 30 min, the ice bath was removed and the mixture was stirred overnight at rt. The mixture was diluted with water (30 mL) and extracted with DCM (2×30 mL). The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by flash chromatograph (40 g silica gel column, 0-40% EtOAc/Heptane) to give tert-butyl 2-(4-bromophenyl)propan-2-ylcarbamate the title compound (1.13 g, 90%): LC/MS (Table 2, Method b) Rt=2.66 min.; MS m/z: 315 (M+H)+. the ice bath was removed The mixture was diluted with water (30 mL) extracted with DCM (2×30 mL) dried over MgSO4 filtered concentrated in vacuo The crude material was purified by flash chromatograph (40 g silica gel column, 0-40% EtOAc/Heptane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2-(4-bromophenyl)-2-methylpropanamide (3 g) in tert-butanol (31 mL) was added [bis(trifluoroacetoxy)iodo]benzene (8 g) portionwise at room temperature. The reaction mixture was stirred at reflux temperature for 30 min Pyridine (3 mL) was added to the mixture. After being stirred at reflux temperature for 1 h, the reaction mixture was concentrated to dryness. The residue was dissolved in benzene and washed with 1 M citric acid aqueous solution (2 times), sodium bicarbonate aqueous solution (5 times) then brine. The organics were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (0-20% ethyl acetate in hexanes) gave the product (3.29 g, 84%). 1HNMR (CDCl3) 400 MHz δ: 7.43 (d, J=8.6 Hz, 2H), 7.27 (d, J=8.6 Hz, 2H), 1.59 (br s, 6H), 1.48-1.05 (m, 9H). was added to the mixture After being stirred at reflux temperature for 1 h the reaction mixture was concentrated to dryness The residue was dissolved in benzene washed with 1 M citric acid aqueous solution (2 times), sodium bicarbonate aqueous solution (5 times) The organics were dried over anhydrous sodium sulfate concentrated under reduced pressure Purification by column chromatography (0-20% ethyl acetate in hexanes)