- January 2015 (12)
- December 2014 (2)
- November 2014 (2)
- September 2014 (4)
- June 2014 (7)
- May 2014 (6)
- March 2014 (1)
- March 2014 (1)
- February 2014 (9)
- January 2014 (7)
- December 2013 (4)
- November 2013 (5)
- September 2013 (14)
- June 2013 (15)
- May 2013 (7)
- April 2013 (19)
- March 2013 (21)
- March 2013 (47)
- February 2013 (19)
- January 2013 (17)
- December 2012 (10)
- November 2012 (12)
- September 2012 (8)
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- June 2012 (14)
- May 2012 (15)
- April 2012 (9)
- March 2012 (4)
- March 2012 (5)
- February 2012 (4)
- - New section - (1)
- Completed Experiments (158)
- Experiments (174)
- MNR101-110 (13)
- MNR111-120 (13)
- MNR51-60 (3)
- MNR61-70 (1)
- MNR81-90 (4)
- MNR91-100 (5)
- mnr121-130 (7)
Starting material - Synthesis of thienopyrimidine MNR89-3
As for Chlorination of MNR89 To Give MNR99-2
Hazard Assessment
Procedure
Reaction carried out in two lots due to scale and volume of POCl3 required.
A
To MNR89-3 (3.95 g, 25.96 mmol) at room temperature was added POCl3 (24 mL, 259 mmol) under argon and the mixture was heated to reflux for 2 hours during which time the reaction turned a dark brown colour. The the reaction was then allowed to reach room temperature and was slowly added dropwise to ice ice (400 mL) in a large beaker. The mixture was then slowly neutralised with sodium bicarbonate. A pale brown solid also began to precipitate out during the quencing. Once the reaction was fully quenched it was extracted with EtOAc (400 mL x 2), the organics were combined and washed with brine (100 mL) then dried with anhydrous magnesium sulfate, filtered and concentrated to give a pale orange solid.
B as above and quenched in the same ice bath, starting material (4.10 g, 26.9 mmol)
Column 40-80% EtOAc/Hex
Fracs 1-5 - 8.269 g, 48.5 mmol, 92% as a white crystaline solid
NMR
Conclusion
Clean porduct in good high yield.
Strings
Starting material
InChI=1S/C6H4N2OS/c9-6-5-4(1-2-10-5)7-3-8-6/h1-3H,(H,7,8,9)
Product
InChI=1S/C6H3ClN2S/c7-6-5-4(1-2-10-5)8-3-9-6/h1-3H
Starting material - JRC13-6
As for compound 10a here and MNR100-1
Hazard Assessment
Procedure
A suspension of JRC13-6 (0.70 g, 4.10 mmol) in morpholine (3.5 mL, 041.0 mmol) was gently heated under reflux for 3 hours and then allowed to cool to room temperature. EtOAC was then added to the mixture to rinse the magnetic stirrer and on doing so a white precipitate formed. More EtOAc (10 mL) was added and the mixture was filtered and the solid washed with hexane.
Col 80% EtOAc/Hex
Frac 7-19 - 0.805 g, 3.63 mmol, 89% as pale yellow, fluffy solid
NMR
Starting Material
Product
Conclusion
Good clean high yielding reaction
Strings
Starting material
InChI=1S/C6H3ClN2S/c7-6-5-4(1-2-10-5)8-3-9-6/h1-3H
Product
InChI=1S/C10H11N3OS/c1-6-15-9-8(1)11-7-12-10(9)13-2-4-14-5-3-13/h1,6-7H,2-5H2
Starting material - MNR99-1
Hazard Assessment
Procedure
A suspension of MNR99-1 (0.15 g, 0.88 mmol) in morpholine (0.75 ml) was gently heated under reflux for 90 minutes (I had to leave the lab ) and then allowed to cool to room temperature overnight (should have been worked up earlier). EtOH (2 mL) was added to the mixture but everything went into solution. The mixture was concentrated and columned.
Column - 20-100% EtOAc/Hex
Fracs 1-25 0.005 g, 0.03 mmol, 3% - starting material
Fracs 36-63 0.169 g, 0.76 mmol, 87% - product
Fracs 64-flush 0.125 g - not clean whatever it is
NMR
Product
Conclusion
Successful reaction to yield the desired product. This can now be tested and also taken on to substitute at the 6 postion either via halogenation followed by suzuki coupling or by direct arylation
Starting material MNR89-1 - 2nd crop
Hazard Assessment
Procedure
To MNR89-1 (2.94 g, 19.32 mmol) at room temperature was added POCl3 (18 mL, 193 mmol) under argon and the mixture was heated to reflux for 90 minutes during which time the reaction turned a dark brown colour. The the reaction was then allowed to reach room temperature and was cooled in an ice bath and slowly queched with some ice followed by saturated sodium bicarbonate solution. During the quenching the mixture was transferred to a 1 L beaker due to volume of solution required. A pale brown solid also began to precipitate out during the quencing. Once the reaction was fully quenched (almost 800 mL aq required) it was extracted with EtOAc (400 mL x 2), the organics were combined and washed with brine (100 mL) then dried with anhydrous magnesium sulfate, filtered and concentrated to give a pale orange solid (2.47 g, 14.5 mmol, 75%)
NMR
NMR showed approx 10% impurities, possibly starting material. No further purification was carried out at this pint.
Strings
Starting material
InChI=1S/C6H4N2OS/c9-6-5-4(1-2-10-5)7-3-8-6/h1-3H,(H,7,8,9)
Product
InChI=1S/C6H3ClN2S/c7-6-5-4(1-2-10-5)8-3-9-6/h1-3H
Starting material MNR89-1 - 2nd crop
As for JRC13-2
Hazard Assessment
Procedure
To MNR89-1 (1.0 g, 6.57 mmol) at room temperature was added POCl3 (6.13 mL, 65.7 mmol) under argon and the mixture was heated to reflux for 90 minutes during which time the reaction turned a dark brown colour. The the reaction was then allowed to reach room temperature and was cooled in an ice bath and slowly queched with some ice followed by saturated sodium bicarbonate solution. During the quenching the mixture was transferred to a 500 mL conical flask due to volume of solution required. A pale brown solid also began to precipitate out during the quencing. Once the reaction was fully quenched (almost 500 mL aq required) it was extracted with EtOAc (200 mL x 2), the organics were combined and washed with brine (75 mL) then dried with anhydrous magnesium sulfate, filtered and concentrated to give a pale orange solid (1.196 g, 7.01 mmol, >100%)
NMR
1H NMR showed product and only slight traces on impurities. No further purification required.
Strings
Starting material
InChI=1S/C6H4N2OS/c9-6-5-4(1-2-10-5)7-3-8-6/h1-3H,(H,7,8,9)
Product
InChI=1S/C6H3ClN2S/c7-6-5-4(1-2-10-5)8-3-9-6/h1-3H