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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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11th March 2013 @ 04:47
Mnr: MNR81-90

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

As for Synthesis of thienopyrimidine MNR89-1

Hazard Assessment

HIRAC MNR89.pdf

Procedure

To methyl-3-aminothiophene-2-carboxylate (11.25 g, 71.6 mmol) and ammonium formate (4.96 g,  78.7 mmol) was added formic acid (2.97 mL, 78.73 mmol) and formamide (15.6 mL, 393 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 watyer and filtered to give an off white solid.   The crude was recrystalised with EtOH (400 ml) to give fine white crystals.

 

1st crop - 4.615 g, 30.3 mmol, 42%

2nd crop - 1.108 g, 7.3 mmol, 10 %

The ethanol was then concentrated to give - 3.15 g, 20.7 mmol, 29%

 

Total recovered - 8.873 g, 58.3 mmol, 81%

 

NMR

mnr89-2_1stcrop_1H.pdf
mnr89-2_crop1.zip

mnr89-2_3rdcrop_1H.pdf
mnr89-2_3rd_crop.zip
2nd crop and concentrated filtrated together - just as clean as the 1st crop

Conclusion

The concentrated filtrate was as clean as the recrystalisation therefore this step was not required unlike in MNR89-1.  In future attempts an NMR of the crude should be taken to judge if a recrystalisatin is required or not.

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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24th January 2013 @ 03:46
Mnr: MNR81-90

Synthesis of thienopyrimidine (MNR89-1) from methyl-3-aminothiophene-2-carboxylate

As for compound 22, Method B

Hazard Assessment

HIRAC MNR89.pdf

Procedure

To methyl-3-aminothiophene-2-carboxylate (9.89 g, 62.9 mmol) and ammonium formate (4.36 g, 69.2 mmol) was added formic acid (2.61 mL, 69.21 mmol) and formamide (13.7 mL, 346 mmol) and the mixture was heated to 140 °C.  After 19 hours, the reaction was cooled to room temperature, filtered and washed with water to give an off white solid that was dried under vacuum (7.5 g).  NMR of this showed desired product with slight traces of impurities.  The crude was recrystalised with EtOH (230 ml) to give fine white crystals.

 

1st crop - 3.075 g, 20.21 mmol, 32 %

2nd crop 3.94 g, 25.89 mmol, 41 %

Total recovered - 7.015 g, 46.1 mmol, 73 %

 

NMR

crude filter

 

mnr89-1_filter_1H.pdf
mnr89-1_filter.zip

1st crop

mnr89-1_1stcrop_1H.pdf
MNR89-1_1stCrop.zip


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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23rd January 2013 @ 07:05
Mnr: MNR81-90

Repeat of conditions and substrates used in JRC50-2 to form the 4-substituted product - MNR86-1

 

Hazard Assessment

HIRAC MNR86.pdf

Procedure

JRC40-2 (0.040 g, 0.17 mmol), 4-sulfamoylphenylboronic acid, pinacol ester (0.054 g, 0.19 mmol), potassium acetate (0.068 g, 0.70 mmol) and PdCl2(dppf) (0.013 g, 0.02 mmol) were dissolved in degassed 20% 1,4-dioxane/H2O (2 mL) (degassed by passing N2 through the solution for about 15 mniutes).  The resulting mixture was heated at reflux for 24 hours at which time TLC still showed starting JRC40-2.  4-sulfamoylphenylboronic acid, pinacol ester (0.054 g, 0.19 mmol) and PdCl2(dppf) (0.013 g, 0.02 mmol) was added to the reaction and refluxing was contiuned overnight.  In the morning the reaction had run dry, ground joint on the condenser wasn't tight.  The reaction was allowed to cool to room temperature, water (2mL) was added and extracted with EtOAc (5 ml x 3), the organics were combined and washed with brine (5 mL) then dried over anhydrous MgSO4, filtered and concentrated to give the crude (0.126 g) as ayellow/red solid.  Recrystallisation was attempted in 50% EtOH/H20 (2.5 mL) as per JRC50-2

TLC

After 15 hours the first TLC was taken.  Cataylst, boronic acid and JRC40-2 were all co-spotted with the reaction mixure (which was given a mini workup with water and EtOAc).  TLC ran in 100% EtOAc and showed both starting materials were still in the reaction mixture and a new lower running spot.

SANY0056.JPG

The reaction was left to stir at reflux.  TLC after 24 hours very similar to this one at 15 hours.

Attached Files