3-[tert-butyl(dimethyl)silyl]oxypropanal

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 anhydrous dimethylsulfoxide (0.05 mole) in anhydrous methylene chloride (100 ml) cooled to 0° C. under nitrogen with stirring is added a solution of oxalyl chloride (0.05 mole) in anhydrous methylene chloride (100 ml). After stirring for 15 minutes, a solution of 1-tert-Butyldimethylsilyloxy-3-hydroxypropane (0.04 mole) in methylene chloride (150 ml) is added over a period of 30 minutes. Then the reaction is quenched by adding triethyl amine (1 mole) slowly. The reaction mixtureis diluted with ethyl acetate (200 ml), washed with water (75 ml), brine (75 ml), dried and concentrated. The product is used as such in the subsequent condensation step. After stirring for 15 minutes Then the reaction is quenched washed with water (75 ml), brine (75 ml) dried concentrated such in the subsequent condensation step

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

Procedure: A mixture of 3-(1-methylindol-3-yl)-4-(3-aminophenyl)-1H-pyrrole-2,5-dione (0.2 g, 6 mmol) and 3-(tert-butyldimethylsilyloxy)propionaldehyde (0.25 g, 13 mmol) in CH2Cl2 (10 mL) and MeOH (5 mL) was stirred at room temperature for 15 min and then NaCNBH3 (57 mg, 1.5 eq) was added. The reaction mixture was stirred at RT overnight and then concentrated under vacuo. The residue was purified by preparatory TLC to give 98 mg 3-(1-methylindol-3-yl)-4-[3-(3-tert-butyldimethylsilyloxypropylamino)phenyl]-1H-pyrrole-2,5-dione (32%) MS (LSIMS): (M+H)+ 490, MP: 58-65° C. The reaction mixture was stirred at RT overnight concentrated under vacuo The residue was purified by preparatory TLC

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

Procedure: Tetrapropylammonium perruthenate (0.18 g, 5.3 mmol) was added to a mixture of methylene chloride (20 mL) and acetonitrile (2 mL) containing 3-(tert-butyldimethylsilyloxy)-propanol (2 g, 0.01 mmol), N-methylmorpholine N-oxide (1.76 g) and 4 Å molecular sieves. The reaction mixture was stirred at RT overnight and then filtered through a pad of silica gel. The filtrate was concentrated under vacuo to afford 3-(tert-butyldimethylsilyloxy)-propionaldehyde (1.3 g, 66%). filtered through a pad of silica gel The filtrate was concentrated under vacuo

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

Procedure: To a solution of anhydrous dimethylsulfoxide (0.05 mole) in anhydrous methylene chloride (100 ml) cooled to 0° C. under nitrogen with stirring is added a solution of oxalyl chloride (0.05 mole) in anhydrous methylene chloride (100 ml). After stirring for 15 minutes, a solution of 1-tert-Butyldimethylsilyloxy-3-hydroxypropane (0.04 mole) in methylene chloride (150 ml) is added over a period of 30 minutes. Then the reaction is quenched by adding triethyl amine (1 mole) slowly. The reaction mixture is diluted with ethyl acetate (200 ml), washed with water (75 ml), brine (75 ml), dried and concentrated. The product is used as such in the subsequent condensation step. After stirring for 15 minutes Then the reaction is quenched washed with water (75 ml), brine (75 ml) dried concentrated such in the subsequent condensation step

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

Procedure: Following the procedures for 519, 8-azetidin-3-yl-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene was reacted with 3-(tert-butyldimethylsilyloxy)propanal to give 526. MS(ESI+) 440.2

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

Procedure: Following the procedures for 519, 8-azetidin-3-yl-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene was reacted with 3-(tert-butyldimethylsilyloxy)propanal to give 526. MS(ESI+) 440.2

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

Procedure: 22.5 ml (113 mmol) of triethyl phosphono-acetate are dissolved in 100 ml of THF. 4.5 g (113 mmol) of 60% sodium hydride are then added, and the medium is stirred for 30 minutes at ambient temperature. A solution of 20 g (75.6 mmol) of 3-(tert-butyldimethylsilanyloxy)propan-1-one in 100 ml of THF is then added drop by drop. The medium is stirred for 6 hours, then treated with water and extracted with ethyl acetate. The residue obtained is purified by chromatography on silica gel (eluent ethyl acetate 10-heptane 90). A yellow oil is obtained (m=7.6 g; Y=30%). The medium is stirred for 6 hours extracted with ethyl acetate The residue obtained is purified by chromatography on silica gel (eluent ethyl acetate 10-heptane 90) A yellow oil is obtained (m=7.6 g; Y=30%)