All Blogs | Help | Support | About
x This LabTrove instance has just been upgraded to 2.3, to see what new check out the documentation, http://www.labtrove.org/documentation/
31st July 2014 @ 07:48

Repeat of TM 37, using straight triethyl orthoformate as solvent/reagent, plus catalytic TsOH, together with a longer reaction time.

scheme

2-chloro-6-hydrazinylpyrazine (from Resynthesis of 2-chloro-6-hydrazinylpyrazine (TM 34-2): assume pure, 300 mg, 2.07 mmol) and tosylic acid (60 mg, 35 mmol, .15 eq) were added to triethyl orthoformate (3 mL), and stirred at reflux (bath temperature 145 oC) for 18 h with an air condenser, under a gently flowing stream of nitrogen. The reaction mixture was then concentrated under a stream of nitrogen, to give a thick dark oil, together with some insoluble black charcoal-looking residue. This was diluted with EtOAc, filtered to remove solid gunk, re-concentrated under reduced pressure, and purified by automatic column chromatography (loaded neat).

Three fractions were obtained, in 40 mg, 80 mg, and 50 mg yield (the loss of mass can likely be attributed to the degraded material discarded earlier, presumably from the high reaction temperature). Fractions one and two were somewhat overlapping, so neither can be considered pure.

 

HIRAC: See TM 37-1

31st July 2014 @ 02:43

GitHub Issue #237

Procedure:

Lithium aluminium hydride (1.9 g, 49.4 mmol, 1.5 equiv.) was dissolved in anhydrous THF (33 mL) and cooled to 0 ˚C. Crude AEW 176-1 (~32.9 mmol) was dissolved in anhydrous THF (33 mL) and added dropwise at 0 ˚C. Reaction mixture stirred at 0 ˚C for 15 min and then removed from the ice bath and stirred whilst reaching rt

 

Data:

 

Hazard and Risk Assessment:

HIRAC AEW 179-1.pdf

 

InChi Key:

InChI=1S/C10H22O3Si/c1-8(9(11)12-5)13-14(6,7)10(2,3)4/h8H,1-7H3

to

InChI=1S/C9H22O2Si/c1-8(7-10)11-12(5,6)9(2,3)4/h8,10H,7H2,1-6H3

Attached Files
31st July 2014 @ 02:26

Repeat synthesis of JU 1-15 as more starting material is needed, conditions from TM 34-2 trialled. 

Reaction Scheme

Procedure

Started 

2,6-Dichloropyrazine (Aldrich, 1.00 g, 6.8 mmol) was dissolved in ethanol (10 mL) to give a clear solution. The solution was heated to 80°C (bath temperature) before hydrazine hydrate (0.35 mL, 360 mg, 7.2 mmol) was added resulting in a pale yellow solution. The resulting mixture was heated at reflux (bath temperature 100˚C) for x h.

 

HIRAC & Risk Assessment

See JU 1-1

InChI strings

InChI=1S/C4H2Cl2N2/c5-3-1-7-2-4(6)8-3/h1-2H

to

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

SMILES

ClC1=CN=CC(Cl)=N1

to

ClC1=CN=CC(NN)=N1

31st July 2014 @ 02:10

Investigation of benzyl ethers since there is little data on them currently (see wiki). I have chosen to attached the difluorophenyl methanol to the triazolopyrazine core with the chloro substituent on the phenyl ring to compare the effect of the ether chain length directly with MMV 639565, which is one CH2 group longer. 

Literature reference: 10.1021/jo901707x

GitHub link: 

Reaction Scheme

Procedure

Started

JU 16-1 (0.065 mL, 82 mg, 0.57 mmol, 1 equiv) was added to 1.5 mL toluene along with JU 8 (150 mg, 0.57 mmol, 1 equiv), potassium hydroxide (105 mg, 1.88 mmol, 3.3 equiv) and 18-crown-6 (8 mg, 0.03 mmol, 0.05 equiv). The reaction mixture turned a dark red-brown on addition of the 18-crown-6. The reaction was stirred at 40°C for 1 h.  

 

HIRAC

HIRAC JU 17-1.pdf

InChI strings

InChI=1S/C11H6Cl2N4/c12-8-3-1-7(2-4-8)11-16-15-10-6-14-5-9(13)17(10)11/h1-6H

and 

InChI=1S/C7H6F2O/c8-6-2-1-5(4-10)3-7(6)9/h1-3,10H,4H2

to

InChI=1S/C18H11ClF2N4O/c19-13-4-2-12(3-5-13)18-24-23-16-8-22-9-17(25(16)18)26-10-11-1-6-14(20)15(21)7-11/h1-9H,10H2

SMILES

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

and

OCC1=CC(F)=C(F)C=C1

to

ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CC=C(F)C(F)=C4)N32

Attached Files
31st July 2014 @ 00:39

GitHub Issue #235 and #236


  

 

Procedure:

Lithium aluminium hydride (1.9 g, 49.4 mmol, 1.5 equiv.) was dissolved in anhydrous THF (33 mL) and cooled to 0 ˚C. Crude AEW 176-1 (~32.9 mmol) was dissolved in anhydrous THF (33 mL) and added dropwise at 0 ˚C.

 

Data:

 

Hazard and Risk Assessment:

HIRAC AEW 178-1.pdf

InChi Key:

InChI=1S/C15H24O3Si/c1-15(2,3)19(5,6)18-13(14(16)17-4)12-10-8-7-9-11-12/h7-11,13H,1-6H3

to

InChI=1S/C14H24O2Si/c1-14(2,3)17(4,5)16-13(11-15)12-9-7-6-8-10-12/h6-10,13,15H,11H2,1-5H3

Attached Files