1,2,2,6,6-pentamethylpiperidin-4-ol

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:6.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound was synthesized strictly under dry and inert reaction conditions. The compound 2-(2′-tert-butyl-di-metylsilyloxy-5′-bromomethylphenyl)benzotriazole (2.1 gms, 0.00501 M) was taken in one 25 mL capacity RB and dissolved in 8 mL dry dimethylformamide (DMF) under Argon atmosphere with stirring. In another two-necked RB, 1,2,2,6,6-pentarnethyl-4-piperidinol (1.0356 gm, 0.00601 M) and sodium hydride (0.3 gms, 0.01252 M) were taken and dissolved in 6 mL dry DMF with stirring under Argon atmosphere. This reaction mixture was agitated for almost 60 min and then cooled to 4-8° C. To this reaction mixture the contents of the first RB was added gradually over a period of 30-60 min. This reaction mixture was further agitated for 2-4 hrs followed by refluxing the same for a period of 2-4 hrs. The contents of the RB were cooled to room temperature and further agitated for 4-6 hrs at room temperature. The solvent in the RB was evaporated under reduced pressure and the solid mass in the RB was dissolved in 15 mL water and repeatedly extracted with dichloromethane (4×10 mL). Dichloromethane was then evaporated under vacuum at 38° C. over a rotavapor to give pale yellow colored crystalline product 2-[2′-tert-butyldimetylsilyloxy-5′-methyleneoxy((1″, 2″, 2″, 6″, 6″-pentamethyl-4″-piperidinyl) phenyl)benzotriazole. The TLC showed very little amount of unreacted starting material. The crude yield was 2.22 gms (87%). The product was purified by recrystalization technique using an appropriate organic solvent to get (83%) yield of pure product. This compound was synthesized strictly under dry inert reaction conditions with stirring under Argon atmosphere This reaction mixture was agitated for almost 60 min To this reaction mixture the contents of the first RB was added gradually over a period of 30-60 min This reaction mixture was further agitated for 2-4 hrs by refluxing the same for a period of 2-4 hrs The contents of the RB were cooled to room temperature further agitated for 4-6 hrs at room temperature The solvent in the RB was evaporated under reduced pressure the solid mass in the RB was dissolved in 15 mL water repeatedly extracted with dichloromethane (4×10 mL) Dichloromethane was then evaporated under vacuum at 38° C. over a rotavapor

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: Mono(2-hydroxyethyl)sebacate and 23.6 g (0.1 mole) 1,2,2,6,6-pentamethylpiperidin-4-ol 17.1 g (0.1 mole) were esterified by heating with 0.4 g toluenesulfonic acid catalyst and 100 cc toluene in a reflux apparatus including a Dean-Stark trap to collect the reaction water as it evolved. When no more water obtained 22.2 g (0.15 mole) triethyl orthoformate was added and heating under reflux continued for 9 hours. Stripping under vacuum removed toluene and excess triethyl orthoformate, and left an oily liquid product represented by formula ##STR49## to collect the reaction water as it

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

Procedure: Mono(2-hydroxyethyl)sebacate and 23.6 g (0.1 mole) 1,2,2,6,6-pentamethylpiperidin-4-ol 17.1 g (0.1 mole) were esterified by heating with 0.4 g toluenesulfonic acid catalyst and 100 cc toluene in a reflux apparatus including a Dean-Stark trap to collect the reaction water as it evolved. When no more water obtained 22.2 g (0.15 mole) triethyl orthoformate was added and heating under reflux continued for 9 hours. Stripping under vacuum removed toluene and excess triethyl orthoformate, and left an oily liquid product represented by formula ##STR49## to collect the reaction water as it

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: NaH (60% in mineral oil, 18 mg, 0.45 mmol) added to a solution of 1,2,2,6,6-pentamethylpiperidin-4-ol (73 mg, 0.43 mmol) in dry DMF (1 mL) at room temperature. This was left stirring for 30 min and then solid 2-((5-cyano-2,4-difluorophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 414) (50 mg, 0.14 mmol) was added. The reaction was left stirring at room temperature for ¾ hr and then heated at 55° C. for 7 hr. It was quenched with sat. aq. NH4C solution (0.5 mL) and diluted with DCM. After washing with water (3×), the organic phase was dried with sodium sulfate. The solvent was removed and radial silica gel chromatography with DCM containing 0 to 3% MeOH and then 1 to 4% 2N NH3 in MeOH afforded the title compound (37 mg) as a glass. This was left The reaction was left stirring at room temperature for ¾ hr It was quenched with sat. aq. NH4C solution (0.5 mL) diluted with DCM After washing with water (3×) the organic phase was dried with sodium sulfate The solvent was removed