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7th May 2013 @ 10:16

Repeat of AT-26-1.

To a solution of isopropanol (4 mL) and potassium carbonate (0.24 mL, 1 M, 0.24 mmol, 2.0 equiv.) degassed with argon was added AT-5 (0.030 g 0.12 mmol, 1.0 equiv.), 4-sulfamoylphenyl boronic acid pinacol ester (0.037 g, 0.13 mmol, 1.1 equiv.) and PdCl2dppf (0.0088 g, 0.012 mmol, 0.1 equiv.) and the reaction mixture heated to 90 C in a microwave reactor (200 W) for 30 minutes. 

The reaction mixture was diluted with methanol (50 mL), filtered through Celite and concentrated under reduced pressure. The residue was purified by flash column chromatography (95:4.5:0.5 dichloromethane:methanol:ammonia).

Attached Files
7th May 2013 @ 02:14

Repeat of AT-20-2

 

A solution of AT-6 (0.030 g, 0.13 mmol, 1.0 equiv.), 3-(4'-methylpiperazine-1-carbonyl)phenyl boronic acid pinacol ester (0.052 g, 0.16 mmol, 1.2 equiv.) and PdCl2dppf (0.019 g, 0.026 mmol, 0.2 equiv.) in isopropanol (2 mL) and K2CO3 (1 M, 0.26 mL, 0.26 mmol, 2.0 equiv.) was heated to 90 C in a microwave reactor (200 W) for 30 minutes. 

The reaction mixture was diluted with methanol (50 mL), filtered through Celite and concentrated under reduced pressure. The residue was purified by flash column chromatography (95:4.5:0.5 dichloromethane:methanol:ammonia) to give the product (0.038 g, 82%) as a brown solid. 

 

HIRAC

AT-Suzuki.pdf

 

1H NMR

AT-20-3.pdf
1H NMR (500 MHz, MeOD) Looks good.

 

In DMSO for solubility:

 

AT-20-3-1H.pdf
 1H

AT-20-3-13C.pdf
 13C
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Attached Files
3rd May 2013 @ 01:42

Precursor to the sulfonamide with a hydrazyl (rather than amino) group on the pyrimidine ring. Reaction performed under higher dilution, lower catalyst loading and less boronic ester. 

 

To a solution of isopropanol (4 mL) and potassium carbonate (0.24 mL, 1 M, 0.24 mmol, 2.0 equiv.) degassed with argon was added AT-5 (0.030 g 0.12 mmol, 1.0 equiv.), 4-sulfamoylphenyl boronic acid pinacol ester (0.037 g, 0.13 mmol, 1.1 equiv.) and PdCl2dppf (0.0088 g, 0.012 mmol, 0.1 equiv.) and the reaction mixture heated to 90 C in a microwave reactor (200 W) for 30 minutes. 

The reaction mixture was diluted with methanol (50 mL), filtered through Celite and concentrated under reduced pressure. The residue was purified by flash column chromatography (95:4.5:0.5 dichloromethane:methanol:ammonia).

HIRAC

AT-Suzuki.pdf
Attached Files
3rd May 2013 @ 00:29

Repeat of AT-20-1. This reaction should work. 

 

A solution of AT-6 (0.030 g, 0.13 mmol, 1.0 equiv.), 3-(4'-methylpiperazine-1-carbonyl)phenyl boronic acid pinacol ester (0.052 g, 0.16 mmol, 1.2 equiv.) and PdCl2dppf (0.019 g, 0.026 mmol, 0.2 equiv.) in isopropanol (2 mL) and K2CO3 (1 M, 0.26 mL, 0.26 mmol, 2.0 equiv.) was heated to 90 C in a microwave reactor (200 W) for 30 minutes. 

The reaction mixture was diluted with methanol (50 mL), filtered through Celite and concentrated under reduced pressure. The residue was purified by flash column chromatography (95:4.5:0.5 dichloromethane:methanol:ammonia). 

Accidentally used DMSO-d6 rather than MeOD for NMR. Not going to recover this. Try again!


HIRAC

AT-Suzuki.pdf
Attached Files
3rd May 2013 @ 00:22

Repeat of AT-8-1, with preferential formation of the arylated product at the bromo-position, rather than the diarylated product. Reaction mixture diluted by half, catalyst loading lowered by half, slight excess of boronic acid.  

To a solution of isopropanol (10 mL) and potassium carbonate (0.802 mL, 1 M, 2.0 equiv.) degassed with argon, was added AT-5 (0.100 g, 0.40 mmol, 1.0 equiv.), phenylboronic acid (0.054 g, 0.44 mmol, 1.1 equiv.) and PdCl2dppf (0.029 g, 0.04 mmol, 0.1 equiv.) and the reaction mixture stirred at 80 C. 

The reaction mixture was diluted with methanol (50 mL), filtered through Celite and concentrated under reduced pressure. The residue was purified by flash column chromatography (6:1 hexanes:ethyl acetate) to give three compounds.  

 

NMR

Least polar compound - desired product.

AT-8-2-f20-32-1H.pdf
1H NMR 

AT-8-2-f20-32-13C.pdf
13C NMR

HIRAC

AT-7-1.pdf
Attached Files