- 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)
- August 2012 (17)
- July 2012 (16)
- 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 - Bromination of MNR89 at the 7 position - MNR118-1
As for Chlorination of MNR89 To Give MNR99-3
NMR reference WO2011093684 (A2) ― 2011-08-04 - page 19 step 3
Hazard Assessment
Procedure
To MNR118-1 (0.180 g, 0.78 mmol) at room temperature was added POCl3 (0.73 mL, 7.79 mmol) under argon and the mixture was heated to reflux for 3 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 (20 mL) in a beaker. The mixture was then slowly neutralised with sodium bicarbonate. Once the reaction was fully quenched it was filtered and washed with water to give a pale brown soild (0.086g)
NMR
Conclusion
NMR showed mainly starting material with less than 5% product. The reaction has therefore started to go but has not had long enough. Reaction needs repeated possibly at a higher temperature and for a longer period of time.
The new peaks in the 1H NMR at 9.17 and 8.80 are of different shifts to that of AT-5-6 (9.02 and 8.06) therefore suggesting that the Br substitution has occurred at the 7 position.
Strings
Starting material
InChI=1S/C6H3BrN2OS/c7-3-1-11-5-4(3)8-2-9-6(5)10/h1-2H,(H,8,9,10)
Product
InChI=1S/C6H2BrClN2S/c7-3-1-11-5-4(3)9-2-10-6(5)8/h1-2H
Starting material from Bromination of MNR113-1 to give MNR115-2
as for - Arylation of MNR101-2 with MNR103-1 to give MNR106-1
repeat of Suzuki Coupling of MNR115 to give MNR116-1 but using clean starting material
Hazard Assessment
Procedure
To a degassed solution of IPA (2 mL) and aqueous potassium carbonate (1 M, 0.34 mL) was added MNR115-2 (0.07 g, 0.17 mmol) and phenylboronic acid (0.025 g, 0.21 mmol) and the reaction mixture further degassed for 5 minutes. Pd(dppf)Cl2 (0.025 g, 0.03 mmol) was added and the reaction mixture stirred at 80 °C overnight (15 hours). The reaction was allowed to cool to room temperature and was filtered through celite and rinsed with MeOH (3 x 15 mL).
column - 40-100% EtOAc/Hex
Fracs 17-53 0.040 g as a sticky gum with some solid.
The product was then triturated with 50% Et2O/Hexane to give an off white solid (0.016 g, 0.04 mmol, 23%)
NMR
Conclusion
NMR not 100% clear/clean. Reaction needs repeated before being sent for testing.
Strings
Starting material
InChI=1S/C17H16BrFN4S/c18-15-9-14-16(24-15)17(21-11-20-14)23-7-5-22(6-8-23)10-12-1-3-13(19)4-2-12/h1-4,9,11H,5-8,10H2
InChI=1S/C6H7BO2/c8-7(9)6-4-2-1-3-5-6/h1-5,8-9H
Product
InChI=1S/C23H21FN4S/c24-19-8-6-17(7-9-19)15-27-10-12-28(13-11-27)23-22-20(25-16-26-23)14-21(29-22)18-4-2-1-3-5-18/h1-9,14,16H,10-13,15H2
Microwave Assisted Arylation of MNR115-2 using MNR103-1 to give MNR120-1
Starting material from Bromination of MNR113-1 to give MNR115-2
and Synthesis of Boronic Acid Pinacol Ester - MNR103-1
as for Arylation of aminobromothienopyrimidine (AT-17-1)
Hazard Assessment
Procedure
MNR115-2 (0.07 g, 0.17 mmol), MNR103-1 (0.058 g, 0.21 mmol) and PdCl2(dppf) (0.025 g, 0.03 mmol) were added to a microwave tube and added was IPA (2 ml) and potasisium carbonate solution (1M) (0.34 ml, 0.34 mmol). The mixture was degassed with argon for 5 mniutes then sealed and heated to 90 °C in the microwave reactor (200 W) for 30 minutes.
NMR
Conclusion
good 1H NMR, sample can be sent for testing
Strings
Starting material
InChI=1S/C12H18BNO4S/c1-11(2)12(3,4)18-13(17-11)9-6-5-7-10(8-9)19(14,15)16/h5-8H,1-4H3,(H2,14,15,16)
InChI=1S/C17H16BrFN4S/c18-15-9-14-16(24-15)17(21-11-20-14)23-7-5-22(6-8-23)10-12-1-3-13(19)4-2-12/h1-4,9,11H,5-8,10H2
Product
InChI=1S/C23H22FN5O2S2/c24-18-6-4-16(5-7-18)14-28-8-10-29(11-9-28)23-22-20(26-15-27-23)13-21(32-22)17-2-1-3-19(12-17)33(25,30)31/h1-7,12-13,15H,8-11,14H2,(H2,25,30,31)
Attempted bromination of MNR99 at the 7 position rather than the 6 position.
As for WO2011093684 (A2) ― 2011-08-04 - page 19 step 2
Starting material - Chlorination of MNR89 To Give MNR99-3
As for Bromination of MNR89 at the 7 position - MNR118-1
Hazard Assessment
Procedure
MNR99-3 (0.30 g, 1.76 mmol) was dissolved in acetic acid (2 ml) (*2 mL was used to make up volume in the reaction tube). Bromine (0.27 mL, 5.27 mmol) was added and the reaction was stirred in a sealed tube at 120 °C for 14 hours. The reaction mixture was cooled to room temperature, no precipitate had formed in the black reaction mixture. The reaction mixture was transfered to a round bottomed flask ans rinsed with DCM (10 mL). The mixture was distilled to remove the DCM then under reduced pressure to remove the acetic acid. Ice was added to the resulting mixture and the solid was filtered off washing with water.
Column
Frac 6-26 - product? not sure why this was not taken further (14/5/2013)
Frac 27-40
NMR
Strings
Starting material
InChI=1S/C6H3ClN2S/c7-6-5-4(1-2-10-5)8-3-9-6/h1-3H
Product
InChI=1S/C6H2BrClN2S/c7-3-1-11-5-4(3)9-2-10-6(5)8/h1-2H
Attempted bromination of MNR89 at the 7 position rather than the 6 position.
As for WO2011093684 (A2) ― 2011-08-04 - page 19 step 2
Starting material - Synthesis of thienopyrimidine MNR89-2
Hazard Assessment
Procedure
MNR89-2 (0.30 g, 1.97 mmol) was dissolved in acetic acid (2 ml) (*2 mL was used to make up volume in the reaction tube). Bromine (0.3 mL, 5.91 mmol) was added and the reaction was stirred in a sealed tube at 120 °C for 14 hours. The reaction mixture was cooled to room temperature and a precipitate had formed in the brown reaction mixture. The reaction mixture was transfered to a round bottomed flask ans rinsed with EtOAc (10 mL). The mixture was distilled to remove the EtOAc then under reduced pressure to remove the acetic acid.
** During the distillation, the reaction mixture bumped across the apparatus. It was decided at this stage to rinse and filter everything. The glassware was washed with EtOAc and water to give a pale brown solid which was dried under vacuum (0.205 g, 1.35 mmol, 68%)
NMR
1H NMR consistent with literature
Conclusion
Title product produced in reasonable yield, taken on to the next step to prove substituion at the correct position.
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/C6H3BrN2OS/c7-3-1-11-5-4(3)8-2-9-6(5)10/h1-2H,(H,8,9,10)