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26th August 2015 @ 05:19

Yield is terrible. Needs optimization.

Reaction started at 17:00.

Reaction Scheme.

 

Procedure

To a solution of 3-bromo-5-chloro-[1,2,4]trizolo[4,3- a]pyrazine (80 mg, 0.34mmol, 1 equiv.) in a co-solvent of toluene(1.2ml), ethanol(0.26ml), and water(1.2ml) was added sodium carbonate (267 mg) followed by Tetrakis(triphenylphosphine)palladium(0) (12 mg) and phenylboronic acid (53 mg) under argon in a flask. The reaction mixture was heated at 80 Celsius degree for 17 hours. TLC showed that reaction was completed.

Saturated ammoniun chloride solution (~20ml) was added to the mixture and extracted with ethyl acetate (70ml*3). The organics were collected in the flask, dried over sodium sulfate and evapotated under reduced pressure to give a yellow solid which was then dired on vacuum. Crude NMR showed purification is needed.

The reaction mixture was dissolved in toluene (~2ml) and purified by conlum machine using PE/EA (50:50) as eluent to give a yellow solid (less 10 mg) which was then dried on vacuum. NMR confirmed that they are the desired products.

 

Data

NMR(crude)

TZ 9-1 crude.pdf

NMR(column fractions. NOTE: both pure and less pure are the desried products)

TZ 9-1 less pure column spot.pdf
TZ 9-1 most pure column spot.pdf

HIRAC

HIRAC TZ9-1.pdf

Strings

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

and
InChI=1S/C6H7BO2/c8-7(9)6-4-2-1-3-5-6/h1-5,8-9H
to
InChI=1S/C11H7ClN4/c12-9-6-13-7-10-14-15-11(16(9)10)8-4-2-1-3-5-8/h1-7H
 
 
 
ClC1=CN=CC2=NN=C(Br)N21
and
OB(C1=CC=CC=C1)O
to
ClC1=CN=CC2=NN=C(C3=CC=CC=C3)N21


Attached Files
26th August 2015 @ 04:59

Reaction started at 17:00.

Reaction scheme

Procedure

A mixture of 3-bromo-5-chloro-[1,2,4]trizolo[4,3- a]pyrazine (80 mg, 0.34 mmol, 1 euqiv.), phenylboronic acids (62 mg, 0.68mmol, 1.5 equiv.), Pd(OAc)2 (0.26 mol %), K3PO4(144 mg, 0.68mmol 2 equiv.) in mixture of isopropanol (1.7 mL) and water (1.7 mL) was stirred at 80°C for overnight. 

The mixture was added to brine and extracted 4 times with ethyl acetate (60ml*4). The solvent was removed under reduced pressure.

 

Data

Crude NMR

TZ 8-1 crude.pdf

HIRAC

HIRAC 8-1.pdf

 

Strings

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

and
InChI=1S/C6H7BO2/c8-7(9)6-4-2-1-3-5-6/h1-5,8-9H
to
InChI=1S/C11H7ClN4/c12-9-6-13-7-10-14-15-11(16(9)10)8-4-2-1-3-5-8/h1-7H
 
 
 
ClC1=CN=CC2=NN=C(Br)N21
and
OB(C1=CC=CC=C1)O
to
ClC1=CN=CC2=NN=C(C3=CC=CC=C3)N21


 

Attached Files
25th August 2015 @ 02:10

Reaction started at 12:50 .

Reaction Scheme:

Procedure:

3-bromo-5-chloro-[1,2,4]trizolo[4,3-a]pyrazine (100mg, 0.428mmol, 1 equiv.) and phenyl boronic acid (78.34mg, 0.643mmol, 1.5 equiv.) were combined in a flask. Catalyst Pd(PPh3) (5mol%, 21.42mmol, 24.75 mg) and K2CO(1.29mmol, 177.6mg, 3 equiv.) were added to the flask. THF (6.06ml) and H2O (0.18ml) were added to the flask. The reaction mixture was then heated at 80 celsius degree for 10 hours under argon atmosphere.

Reaction was monitored by TLC. 

Water (~15ml) was added to the reaciton mixture and the mixture was extracted with ethyl acetate (80ml*3). The combined organics were washed with brine (~10ml), dried over sodium sulfate and evaporated under reduced pressure to give yellow oil. The yellow oil was then dried on vacuum.

NMR of the crude showed that purification is needed. The yellow oil was dissolved in toluene(~2ml) and purified by automatic column machine (50% ethly acetate in hexane) to give a yellow solid(43mg, yield 44%).

Data

NMR(crude)

TZ 7-2 crude.pdf

NMR(columned)

TZ 7-2 columned.pdf

HIRAC

see TZ 7-1

Strings

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

and
InChI=1S/C6H7BO2/c8-7(9)6-4-2-1-3-5-6/h1-5,8-9H
to
InChI=1S/C11H7ClN4/c12-9-6-13-7-10-14-15-11(16(9)10)8-4-2-1-3-5-8/h1-7H
 
 
 
ClC1=CN=CC2=NN=C(Br)N21
and
OB(C1=CC=CC=C1)O
to
ClC1=CN=CC2=NN=C(C3=CC=CC=C3)N21


Attached Files
25th August 2015 @ 01:46

Experiment started 25/8/15.

Aim of this experiment is to perform nucleophilic aromatic substitution involving phenylethanol, displacing the Cl on the upper left hand corner of the compound produced in BSX 2-1.

Strings

SMILES

ClC1=CN=CC2=NN=C(C3=CC(F)=CC(F)=C3)N21

and

OCCC1=CC=CC=C1

to

FC1=CC(F)=CC(C2=NN=C3N2C(OCCC4=CC=CC=C4)=CN=C3)=C1

 

InChi

InChI=1S/C11H5ClF2N4/c12-9-4-15-5-10-16-17-11(18(9)10)6-1-7(13)3-8(14)2-6/h1-5H

and

InChI=1S/C8H10O/c9-7-6-8-4-2-1-3-5-8/h1-5,9H,6-7H2

to

InChI=1S/C19H14F2N4O/c20-15-8-14(9-16(21)10-15)19-24-23-17-11-22-12-18(25(17)19)26-7-6-13-4-2-1-3-5-13/h1-5,8-12H,6-7H2

Attached Files
21st August 2015 @ 02:10

In this case, perhaps the selectivity of the bromination on the SM was switched due to the addition of acetic acid as catalyst accroding to the crude NMR result.

Lost in the column. Need to repeat.

Reaction started at 12:30 on August 21st,2015.

Procedure:

NBS was recrystallized before the reaction. Water (50ml) was added to NBS (1g). The mixture was stirred and heated at 100 celsius degree until NBS was dissolved to make a homogeneous orange solution. The solution was then cooled down to room temperature. Bright white crystals crystallized in the solution. The crystals were then filtered out and washed with ice water. 

5-Chloro-[1,2,4]triazolo[4,3-a]pyrazine (100 mg, 0.65mmol, 1 equiv.) and NBS (116 mg, o.65mmol, 1 euqiv.) was combined in a flask. Acetic acid (20 mol%) was added to the reaction mixture as catalyst. Chloroform (5ml) was added to the flask. Reaction mixture was stirred at room temperature for 20 minutes and then heated at reflux. Reaction was monitored by TLC. TLC showed that there were still a large amount of SM left in the reaction mixture. Extra NBS (58 mg, 0.33 mmol, 0.5 equiv.) was added to the reaction mixture.

The reaction mixture was diluted with chloroform and washed with saturated sodium carbonate. The aqueous layer was re-extracted with chloroform. The organics was collected and washed with water, then seperated and dried with sodium sulfate. The solvent was removed under reduced pressure to give a brown solid.  Crude NMR showed that desired product was made and purification was needed. The brown solid was purified by column machine using PE/EA (PE:EA=50:50) as eluent to give a ??.

Lost in the column. Need to repeat.

Data

Crude NMR

TZ 4-5 crude.pdf

HIRAC

see TZ 4-2

Strings

ClC1=CN=CC2=NN=CN21
to 
ClC1=CN=CC2=NN=C(Br)N21
 
InChI=1S/C5H3ClN4/c6-4-1-7-2-5-9-8-3-10(4)5/h1-3H
to
InChI=1S/C5H2BrClN4/c6-5-10-9-4-2-8-1-3(7)11(4)5/h1-2H
Attached Files