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22nd May 2015 @ 15:54

Reaction Scheme 

Experimental Procedure

To a solution of compound JS 15-1 (12 mg, 0.03 mmol) in CH2Cl2 (1 mL) was added iodosobenzene diacetate (11 mg,  0.035 mmol). The reaction was stirred at room temperature and was monitored by TLC. After one hour the reaction was complete as indicated by TLC. The reaction was washed with NaHCO3 (1 mL) and the layers separated. The water layer was extracted with CH2Cl2 (3 x 2 mL) and the combined organic layers were then dried over MgSO4 before the solution was filtered and the solvents removed under reduced pressure. The crude product was purified using dry flash column chromatography (Hexane/EtOAc : 30/1 à 5/2) to give the desired product as a white solid (11 mg, 0.027 mmol, 92%). 1H NMR (601 MHz, CDCl3) δ 10.91 – 10.85 (m, 1H), 8.47 (s, 1H), 8.38 (d, J = 8.7, 2H), 8.30 (d, J = 7.7, 2H), 7.88 (d, J = 8.7, 2H), 7.74 (d, J = 8.4, 1H), 7.57 (d, J = 8.0, 1H), 6.93 (s, 1H).

SMILES 

1. O=C(NC1=CC(C(F)(F)F)=NC=C1)C2=CC=CC(N/N=C/C3=CC=C(C#N)C=C3)=N2

to

2. O=C(NC1=CC(C(F)(F)F)=NC=C1)C2=CC=CC3=NN=C(C4=CC=C(C#N)C=C4)N32

InChI Strings 

1. InChI=1S/C20H13F3N6O/c21-20(22,23)17-10-15(8-9-25-17)27-19(30)16-2-1-3-18(28-16)29-26-12-14-6-4-13(11-24)5-7-14/h1-10,12H,(H,28,29)(H,25,27,30)/b26-12+

to

2. InChI=1S/C20H11F3N6O/c21-20(22,23)16-10-14(8-9-25-16)26-19(30)15-2-1-3-17-27-28-18(29(15)17)13-6-4-12(11-24)5-7-13/h1-10H,(H,25,26,30)

NMR

16-1 nmr.png
Attached Files
22nd May 2015 @ 15:45

Reaction Scheme 

Experimental Procedure

The general procedure of Ubels was followed. To a solution of 6-hydrazinyl-N-(2-(trifluoromethyl)pyridin-4-yl)picolinamide (65 mg, 0.22 mmol) in MeCN (1 mL) was added 4-cyanobenzaldehyde (28 mg, 0.22 mmol) and a drop of acetic acid. The reaction was stirred at reflux for 2 hours upon which the reaction reached completion as indicated by TLC. The reaction mixture was cooled to room temperature and the solvents were removed in vacuo to afford the desired product as a crude white solid (25 mg, 0.07 mmol, 30%), taken on without characterisation. 

SMILES 

1. O=C(NC1=CC=NC(C(F)(F)F)=C1)C2=CC=CC(NN)=N2

to

2. O=C(NC1=CC(C(F)(F)F)=NC=C1)C2=CC=CC(N/N=C/C3=CC=C(C#N)C=C3)=N2

InChI Strings 

1. InChI=1S/C12H10F3N5O/c13-12(14,15)9-6-7(4-5-17-9)18-11(21)8-2-1-3-10(19-8)20-16/h1-6H,16H2,(H,19,20)(H,17,18,21)

to

2. InChI=1S/C20H13F3N6O/c21-20(22,23)17-10-15(8-9-25-17)27-19(30)16-2-1-3-18(28-16)29-26-12-14-6-4-13(11-24)5-7-14/h1-10,12H,(H,28,29)(H,25,27,30)/b26-12+

Attached Files
22nd May 2015 @ 15:20

Reaction Scheme

Experimental Procedure

JS 18-1 [Synthesis of 4-(5-chloro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzonitrile (JS 18-1)] (308 mg, 0.1.21 mmol) was dissolved in toluene (7.5 mL) and then treated with -(3,4-difluorophenyl)ethanol (250 mg, 1.58 mmol). KOH (219 mg, 3.9 mmol) & 18-crown-6 (32 mg, 0.121 mmol) were then added and the mixture was allowed to stir for 1 hour. The reaction was monitored by TLC (100% EtOAc) and after 1 h the starting materials had not fully been consumed. Stirring for a further four hours showed that product had formed but starting material was still present

The mixture was cooled to room temperature before water (15 mL) was added. The phases were separated and the aqueous layer was washed with EtOAc (4 x 15 mL). The organic layer was then washed with water until the aqueous later became neutral. The combined organic layers were dried over Na2SO4 and filtered before removing solvents in vacuo to produce the crude product. The crude was purified using dry flash column chromatography (30/1 --> 1/30 Hexane/EtOAc) to yield the titled compound as a white solid ( 184 mg, 0.49 mmol, 41% yield).

SMILES

1. ClC1=CC=CC2=NN=C(C3=CC=C(C#N)C=C3)N21

to

2. FC1=C(F)C=CC(CCOC2=CC=CC3=NN=C(C4=CC=C(C#N)C=C4)N32)=C1

InChI Strings

1. InChI=1S/C13H7ClN4/c14-11-2-1-3-12-16-17-13(18(11)12)10-6-4-9(8-15)5-7-10/h1-7H

to

2. InChI=1S/C21H14F2N4O/c22-17-9-6-14(12-18(17)23)10-11-28-20-3-1-2-19-25-26-21(27(19)20)16-7-4-15(13-24)5-8-16/h1-9,12H,10-11H2

NMR

JS 21-1 new.png
Attached Files
9th May 2015 @ 09:33

AEW 205-1 (300 mg, 1.0 mmol, 1 equiv) was added to toluene (6 mL) along with AEW 184-2 (154 mg, 1.0 mmol, 1 equiv), potassium hydroxide (199 mg, 3.5 mmol, 3.5 equiv) and 18-crown-6 (19 mg, 0.07 mmol, 0.07 equiv).

The reaction was stirred at room temp for ten minutes and then heated to 40°C (bath temperature) for 1 h.

 

The sample was cooled to room temperature and diluted with 8 mL of water. The mixture was extracted with EtOAc (3 x 20 mL). The combined organic layer was washed with water (1 x 10 mL) until the aqueous layer became neutral followed by brine (5 mL) and dried over MgSO4 and then filtered. 

 

Data:

 

InChi:

InChI=1S/C11H9ClF2N4O/c1-7(3-2-4-19-11(13)14)10-17-16-9-6-15-5-8(12)18(9)10/h2-3,5-6,11H,1,4H2/b3-2-

and

InChI=1S/C9H12O2/c1-11-9(7-10)8-5-3-2-4-6-8/h2-6,9-10H,7H2,1H3

to

InChI=1S/C21H18F2N4O3/c1-28-17(14-5-3-2-4-6-14)13-29-19-12-24-11-18-25-26-20(27(18)19)15-7-9-16(10-8-15)30-21(22)23/h2-12,17,21H,13H2,1H3

 

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

and

OCC(OC)C1=CC=CC=C1

to

FC(F)OC(C=C1)=CC=C1C2=NN=C3N2C(OCC(OC)C4=CC=CC=C4)=CN=C3

8th May 2015 @ 04:35

reaction

Procedure:

SGS 2-1 (1.43 g, 5.6 mmol) was dissolved in DCM (70 mL) and stirred with PIDA (1.77 g, 5.5 mmol) overnight.  Solvent was removed in vacuo

After 24 hours, the solution had turned dark orange and an initial TLC was performed in DCM (Rf = 0.7), and a subsequent TLC was then run in EtOAc with 3% MeOH (Rf = 0.75).  

Conducted by Jason Chami, Evan Hockings, James Kalas, James Manton-Hall, Andreas Orsmond, Mackenzie Shaw and Alex Su.

 

InChI=1S/C12H6ClN5/c13-10-6-15-7-11-16-17-12(18(10)11)9-3-1-8(5-14)2-4-9/h1-4,6-7H

 

TLC

SGS 7-1 tlc