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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
29th January 2015 @ 16:10

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)]  (200 mg, 0.788 mmol) was dissolved in toluene (5.5 mL) and then treated with phenylethyl alcohol (0.12 mL, 0.95 mmol). KOH (145 mg, 2.6 mmol) & 18-crown-6 (24 mg, 0.078 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 two 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 (100/00 --> 00/100 Hexane/EtOAc) to yield the titled compound as a white solid ( 94 mg, 0.27 mmol, 34.6% yield). 

SMILES 

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

to

2. N#CC(C=C1)=CC=C1C2=NN=C3C=CC=C(OCCC4=CC=CC=C4)N32

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/C21H16N4O/c22-15-17-9-11-18(12-10-17)21-24-23-19-7-4-8-20(25(19)21)26-14-13-16-5-2-1-3-6-16/h1-12H,13-14H2

NMR

JS 20-1 MeOH.png
Attached Files
20th January 2015 @ 13:36

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)]  (240 mg, 0.945 mmol) was dissolved in toluene (6 mL) and then treated with 2-(2-chlorophenyl)ethanol (0.15 mL, 1.131 mmol). KOH (174 mg, 3.12 mmol) & 18-crown-6 (27 mg, 0.096 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 been consumed. 

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 (100% EtOAc) to yield the titled compound as a white solid ( 271 mg, 0.723 mmol, 76.5% yield). 

SMILES 

ClC(C=CC=C1)=C1CCOC2=CC=CC3=NN=C(C4=CC=C(C#N)C=C4)N32

to

ClC(C=CC=C1)=C1CCOC2=CC=CC3=NN=C(C4=CC=C(C#N)C=C4)N32

InChI Strings 

InChI=1S/C21H15ClN4O/c22-18-5-2-1-4-16(18)12-13-27-20-7-3-6-19-24-25-21(26(19)20)17-10-8-15(14-23)9-11-17/h1-11H,12-13H2

to

InChI=1S/C21H15ClN4O/c22-18-5-2-1-4-16(18)12-13-27-20-7-3-6-19-24-25-21(26(19)20)17-10-8-15(14-23)9-11-17/h1-11H,12-13H2

TLC 

JS 19-1 TLC.JPG

NMR

JS 19-1 C.png

JS 19-1.png
Attached Files