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25th March 2013 @ 05:50

Performed concurrently with AT-5-5.

 

To AT-5 (2.10 g, 12.3 mmol, 1.0 equiv.) in THF (120 mL) at -78 C was added n-BuLi (7.38 mL, 18.5 mmol, 1.5 equiv.) dropwise and the reaction mixture stirred at -78 C for 30 minutes. Bromine (1.26 mL, 24.6 mmol, 2.0 equiv.) was added dropwise and the reaction mixture warmed to rt and stirred for 1 h. 

The reaction mixture was diluted with an aqueous solution of sodium thiosulfate (150 mL) and extracted into ethyl acetate (3 x 100 mL). The combined organic extracts were dried (MgSO4), concentrated under reduced pressure and the residue purified by flash column chromatography (7:1 hexanes:ethyl acetate) to give starting material AT-1 (0.115 g, 5%) and product AT-5 (1.86 g, 64% based on RSM).

 

HIRAC

AT-5-1.pdf
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25th March 2013 @ 05:45

Performed concurrently with AT-5-6. 

 

 

To AT-5 (2.00 g, 11.7 mmol, 1.0 equiv.) in THF (120 mL) at -78 C was added n-BuLi (7.03 mL, 17.6 mmol, 1.5 equiv.) dropwise and the reaction mixture stirred at -78 C for 30 minutes. Bromine (1.20 mL, 23.4 mmol, 2.0 equiv.) was added dropwise and the reaction mixture warmed to rt and stirred for 1 h. 

The reaction mixture was diluted with an aqueous solution of sodium thiosulfate (150 mL) and extracted into ethyl acetate (3 x 100 mL). The combined organic extracts were dried (MgSO4), concentrated under reduced pressure and the residue purified by flash column chromatography (7:1 hexanes:ethyl acetate) to give the product AT-5 (1.65 g, 56%).

 

HIRAC

AT-5-1.pdf
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25th March 2013 @ 04:30
Mnr: MNR81-90

Synthesis of thienopyrimidine (MNR89-2) from methyl-3-aminothiophene-2-carboxylate

As for Synthesis of thienopyrimidine MNR89-1

Synthesis of thienopyrimidine MNR89-2

Hazard Assessment

HIRAC MNR89.pdf

Procedure

To methyl-3-aminothiophene-2-carboxylate (13.59 g, 86.46 mmol) and ammonium formate (6.0 g, 95.1 mmol) was added formic acid (3.59 mL, 95.1 mmol) and formamide (18.89 mL, 475 mmol) and the mixture was heated to 140 °C.  After 15 hours the reaction was cooled to room temperature and a solid formed.  This was washed with water and filtered to give an off white solid. The crude was recrystalised with EtOH (400 ml) to give fine white crystals.

 

NMR

mnr89-3_filter_1H.pdf
mnr89-3_filter_13C.pdf
mnr89-3_filter.zip
 

Conclusion


Strings


Starting Material

InChI=1S/C6H7NO2S/c1-9-6(8)5-4(7)2-3-10-5/h2-3H,7H2,1H3

InChI=1S/CH3NO/c2-1-3/h1H,(H2,2,3)

Product

InChI=1S/C6H4N2OS/c9-6-5-4(1-2-10-5)7-3-8-6/h1-3H,(H,7,8,9)

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18th March 2013 @ 08:34

Microwave-assisted arylation of AT-6.

 

A solution of AT-6 (0.020 g, 0.87 mmol, 1.0 equiv.), 4-(dimethylamido)phenyl boronic acid pinacol ester(0.029 g, 0.10 mmol, 1.2 equiv.) and PdCl2dppf (0.013 g, 0.018 mmol, 0.2 equiv.) in isopropanol (2 mL) and K2CO3 (1 M, 0.17 mL, 0.17 mmol, 2.0 equiv.) was heated to 80 C in a microwave reactor (200 W) for 30 minutes. 

The reaction mixture was cooled, diluted with methanol (10 mL) and filtered through Celite. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography (95:45:0.5 dichloromethane:methanol:ammonia) to give the product as a brown solid (0.023 g, 88%). Some starting material was observed; the reaction may need a little longer in the microwave (45 minutes?).

Maybe we should get our own microwave... 

NMR

AT-17-1.pdf
1H NMR

AT-17-1-13C.pdf
13C{1H} NMR

  

HIRAC

AT-17-1.pdf
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18th March 2013 @ 04:41

Repeat of AT-10-1, under microwave conditions. 

A solution of AT-6 (0.020 g, 0.87 mmol, 1.0 equiv.), 4-sulfamoylphenyl boronic acid (0.030 g, 0.10 mmol, 1.2 equiv.) and PdCl2dppf (0.013 g, 0.018 mmol, 0.2 equiv.) in isopropanol (2 mL) and K2CO3 (1 M, 0.17 mL, 0.17 mmol, 2.0 equiv.) was heated to 80 C in a microwave reactor (200 W) for 30 minutes. 

The reaction mixture was cooled, diluted with methanol (10 mL) and filtered through Celite. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography (95:45:0.5 dichloromethane:methanol:ammonia) to give the product as a brown solid (0.007 g, 26%). Hm. Not sure what happened here. 

 

NMR

AT-10-4.pdf

 

HIRAC

AT-10-4.pdf
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