4-(TERT-BUTYLDIMETHYLSILYLOXY)CYCLOHEXA&

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 2-iodoaniline (2.5 g, 10.9 mmol) in dichloromethane (160 mL) was added 4-(tert-butyldimethylsilanyloxy)cyclohexanone (2.39 g, 10.9 mmol) and acetic acid (8 mL). After the reaction was stirred for 1 hour at room temperature, sodium triacetoxyborohydride (3.47 g, 16.4 mmol) was added and the reaction was stirred at room temperature overnight. The reaction was quenched with saturated sodium bicarbonate and extracted with dichloromethane. The organic solution was dried (MgSO4) and concentrated to give 4.47 g of the desired amine, which was used without further purification. LC-MS (C15H30INOSi calc'd 431) m/z 432 (M+H). the reaction was stirred at room temperature overnight The reaction was quenched with saturated sodium bicarbonate extracted with dichloromethane The organic solution was dried (MgSO4) concentrated

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

Procedure: (4-Trifluoromethoxy-3-trifluoromethyl-phenyl)-amine (735 mg, 3 mmol) and 4-(tert-butyl-dimethyl-silyloxy)-cyclohexanone (685 mg, 3 mmol) were dissolved in dichloromethane (25 mL). Next, sodium triacetoxyborohydride (1.27 g, 6 mmol) was added. The resulting mixture was stirred at room temperature for 6 days. Afterward, the mixture was diluted with dichloromethane (25 mL), washed with water (20 mL), washed with HCl 1N (20 mL), washed with water (20 mL), and washed with brine (20 mL). The organic layer was collected, dried over magnesium sulfate, filtered, and concentrated under vacuum to afford an oily residue. The residue was purified by column chromatography on silica gel (pentane/ether gradient). The desired product was isolated as a colorless oil (900 mg of 1:1 mixtures of cis and trans isomers, 66% yield). washed with water (20 mL) washed with HCl 1N (20 mL) washed with water (20 mL) washed with brine (20 mL) The organic layer was collected dried over magnesium sulfate filtered concentrated under vacuum to afford an oily residue The residue was purified by column chromatography on silica gel (pentane/ether gradient)

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

Procedure: (4-Trifluoromethoxy-3-trifluoromethyl-phenyl)-amine (735 mg, 3 mmol) and 4-(tert-butyl-dimethyl-silyloxy)-cyclohexanone (685 mg, 3 mmol) were dissolved in dichloromethane (25 mL). Next, sodium triacetoxyborohydride (1.27 g, 6 mmol) was added. The resulting mixture was stirred at room temperature for 6 days. Afterward, the mixture was diluted with dichloromethane (25 mL), washed with water (20 mL), washed with HCl 1N (20 mL), washed with water (20 mL), and washed with brine (20 mL). The organic layer was collected, dried over magnesium sulfate, filtered, and concentrated under vacuum to afford an oily residue. The residue was purified by column chromatography on silica gel (pentane/ether gradient). The desired product was isolated as a colorless oil (900 mg of 1:1 mixtures of cis and trans isomers, 66% yield). washed with water (20 mL) washed with HCl 1N (20 mL) washed with water (20 mL) washed with brine (20 mL) The organic layer was collected dried over magnesium sulfate filtered concentrated under vacuum to afford an oily residue The residue was purified by column chromatography on silica gel (pentane/ether gradient)

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

Procedure: Phosphorus oxychloride(4.08 mL) was added to cooled (−10° C.) N,N-dimethylformamide (20 mL). The temperature was maintained below 0° C. Stirring was continued for another 30 minutes before the addition of 4-(tert-butyldimethylsilyloxy)cyclohexanone (10 g). The mixture was then stirred at room temperature for 2 hours before it was diluted with ethyl acetate (300 mL) and washed with water (3×), brine and dried over Na2SO4. After filtration and concentration, the crude product was used directly in the next reaction without further purification. The temperature was maintained below 0° C The mixture was then stirred at room temperature for 2 hours before it washed with water (3×), brine dried over Na2SO4 After filtration and concentration the crude product was used directly in the next reaction without further purification

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

Procedure: Phosphorus oxychloride(4.08 mL) was added to cooled (−10° C.) N,N-dimethylformamide (20 mL). The temperature was maintained below 0° C. Stirring was continued for another 30 minutes before the addition of 4-(tert-butyldimethylsilyloxy)cyclohexanone (10 g). The mixture was then stirred at room temperature for 2 hours before it was diluted with ethyl acetate (300 mL) and washed with water (3×), brine and dried over Na2SO4. After filtration and concentration, the crude product was used directly in the next reaction without further purification. The temperature was maintained below 0° C The mixture was then stirred at room temperature for 2 hours before it washed with water (3×), brine dried over Na2SO4 After filtration and concentration the crude product was used directly in the next reaction without further purification

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 7-bromo-2-chloro-5-trityl-5H-pyrrolo[3,2-d]pyrimidine (2.00 g, 3.2 mmol) in THF (20 mL) was added a 2.5 N solution of BuLi in hexane (2.82 mL, 7.04 mmol) at −78° C. Then 4-((tert-butyldimethylsilyl)oxy)cyclohexanone (1.2 mL) was added after 15 min. The reaction was stirred at −78° C. for 3 hour, quenched with brine and extracted with EtOAc (3×). The combined organic layer was dried (MgSO4), filtered and concentrated. The residue was purified by ISCO to provide the desired product (1.52 g, 76%). 1H NMR (400 MHz, CDCl3, two isomers) δ 7.64-7.56 (m, 1H), 7.44-7.41 (m, 1H), 7.35-7.31 (m, 9H), 7.16-7.10 (m, 6H), 3.73-3.68 (m, 1H), 2.55-2.51 (m, 1H), 2.42-2.30 (m, 1H), 2.28-2.19 (m, 1H), 2.07-1.94 (m, 2H), 1.91-1.82 (m, 2H), 1.76-1.62 (m, 2H), 0.82 (s, 9H), 0.01 (s, 6H). quenched with brine extracted with EtOAc (3×) The combined organic layer was dried (MgSO4) filtered concentrated The residue was purified by ISCO