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25th August 2016 @ 06:28

Procedure

HM7-1(80 mg, 339.39µmol, 1.0 equiv.), potassium hydroxide (66.65mg, 1.19mmol, 3.5 equiv.) and 18-crown-6 (6.28mg, 23.76µmol, 0.07 equiv.) were stirred in toluene (5 mL) and AEW alcohol (59.04mg, 373.33µmol, 1.1 equiv.) was added and the reaction mixture stirred at rt for 30 mins.


Water (20 mL) was added and the mixture was extracted with EtOAc (3 x 40 mL). Combined organic layers were washed with water (20 mL), brine (20 mL), dried (MgSO4) filtered and evaporated then purified by flash column chromatography using the Biotage IsoleraTM

Log

25th Aug

The reaction started at 4:00pm and left under room temperature overnight.

26th Aug

TLC was performed (75% EtOAc in petroleum) showing that the reaction has yet gone completion. Warm up. 

 

HIRAC

HM 8-1.docx

String

from

InChI=1S/C12H14ClN3/c13-9-5-4-6-10-11(9)12(15-14-10)16-7-2-1-3-8-16/h4-6,11H,1-3,7-8H2

and

InChI=1S/C8H8F2O/c9-7-2-1-6(3-4-11)5-8(7)10/h1-2,5,11H,3-4H2

to

InChI=1S/C20H21F2N3O/c21-15-8-7-14(13-16(15)22)9-12-26-18-6-4-5-17-19(18)20(24-23-17)25-10-2-1-3-11-25/h4-8,13,19H,1-3,9-12H2

Attached Files
24th August 2016 @ 01:49

Procedure

The ratio between the reactants in this flask was as follows:50mg of 3-bromo-5-chloro-[1,2,4]triazolo[4,3-a]pyrazine(214µmol,1equiv.),6.16mg of Pd(dba)2(21.42µmol, 0.05equiv.), 33.21mg of Pd(dba)2(10.71µmol, 0.05equiv.) 36.90mg of piperazine (428.35µmol, 1.2equiv),30.87mg of t-BuONa(642.53µmol, 1.5equiv.),4.47mg of JohnPhos(14.99µmol,0.07equiv.) The reactants were placed in the flask and purged with argon then 2ml of toluene was added.The mixture was purged with argon again and stirred under argon at room temperature.The reaction will be monitored by TLC

 

HIRAC

HM 6-3.docx


Log

24th Aug

The reaction started at 3:10pm.After an hour, the reaction had gone completion.

TLC was perfomed(25%EtOAc in petroleum)

It looked like ,the product could be the base line spot


Attached Files
24th August 2016 @ 01:46

Procedure

The ratio between the reactants in this flask was as follows:250mg of 3-bromo-5-chloro-[1,2,4]triazolo[4,3-a]pyrazine(1.07mmol,1equiv.),30.79mg of Pd(dba)2(53.54µmol, 0.05equiv.), 33.21mg of Pd(dba)2(10.71µmol, 0.05equiv.) 109.42mg of piperadine (1.29mmol,126.94mml,  1.2equiv),154.37mg of t-BuONa(1.61mmol, 1.5equiv.),46.68mg of BINAP(74.96µmol,0.07equiv.) The reactants were placed in the flask and purged with argon then 2ml of toluene was added.The mixture was purged with argon again and stirred under argon at room temperature.The reaction will be monitored by TLC

Log

24th Aug

The reaction started at 3:20pm. After an hour, the reaction had almost gone completion according to TLC(25%of EtOAc in petroleum) There was still a small amout of SM so the reaction was left overnight.

25th Aug

The reaction mixure was diluted with 50ml of EtOAc and washed with 10ml of water. The aquaous layer was washed with EtOAc(2x15ml). And the oganic was conbined and concentrated (After working up, TLC looks different)then columned to yield 109mg orange powder. (Yield :43%)

 

 

 

HIRAC

HM 7-1.docx
Attached Files
22nd August 2016 @ 02:46

Procedure

20mg of HM3-2 was placed in the vial then 4ml of benzene was added to form a  homogeneous yellow solution. The top of the vial was covered with perforated parafilm and left over weekend. Several  single crystals was formed.

 

HIRAC 

Recrystalisation.docx
Linked Entries
Attached Files
18th August 2016 @ 00:49

Reference:Organic Process Research & Development 2006, 10, 762-769

Procedure:

The ratio between the reactants in this flask was as follows:100mg of 3-bromo-5-chloro-[1,2,4]triazolo[4,3-a]pyrazine(428.35µmol,1equiv.) ,12.32mg of Pd(dba)2(21.42µmol,0.05equiv.),33.21mg of piperazine(385.52µmol,0.9equiv),61.75mg of t-BuONa(642.53µmol,1.5equiv.),20.00mg of BINAP(32.13µmol,0.07equiv.) The reactants were dissolved/suspended in 2ml of toluene and stirred under Nat room temperature.The reaction will be monitored by TLC

HIRAC

HM 6-2.docx

 

String

From 

InChI=1S/C5H2BrClN4/c6-5-10-9-4-2-8-1-3(7)11(4)5/h1-2H

to

InChI=1S/C9H11ClN6/c10-7-5-12-6-8-13-14-9(16(7)8)15-3-1-11-2-4-15/h5-6,11H,1-4H2

Log

18th Aug

The reaction started at 2:10pm. Solid reactants were added to the flask then purged with argon. Afterwards, toluene was added, and mixture was purged again with argon. 

TLC was performed at 4:00pm under condition of 25%ethyl acetate in petroleum. The SM consuming step was quite fast even if it's under RT. quite a lot of the SM was consumed, and many byproducts formed.  One of the top spots was assumed to be BINAP. Reaction was left overnight.

19th Aug

TLC was performed(50%ethy acetate in petroleum) at 10:00am.The SM spot was gone. No other obvious difference from the one performed yestaday. Reaction was warmed up to 40℃.

TLC was performed under the same condition at 11:30am. Obviously, there was no SM left. and main product looked like the top spot which could be SM coupled with itself when considering that only 0.9equiv of piperazine was added. 

 

23th Aug

The reaction was switched off and the mixture was concentrated and then columned.

4 fraction was collected yet in so small amout that the first two fraction was difficult to scratch off from the flask. Fraction 3 was not soluable in CDCl3 thus almost no signle in the spectrum. This one needs repeating in DMSO.Fraction 4 looks quite promising.

 

NMR data

HM 6-2 frac 4.pdf
HM 6-2 frac 4.zip
Attached Files