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30th October 2015 @ 01:30

 

AEW 245-1 (200 mg, 0.59 mmol, 1 equiv) was added to toluene (3.8 mL) along with AEW 221-1 (132 mg, 0.59 mmol, 1 equiv), potassium hydroxide (116 mg, 2.10 mmol, 3.5 equiv) and 18-crown-6 (11 mg, 0.04 mmol, 0.07 equiv).

The reaction was stirred at room temp for ten minutes and then heated to 40°C (bath temperature) for 3 h. TLC showed no SM and baseline spots.

The sample was cooled to room temperature and diluted with 4 mL of water. The mixture was extracted with EtOAc (3 x 10 mL). The combined organic layer was washed with water (1 x 4 mL) until the aqueous layer became neutral followed by brine (3 mL) and dried over Na2SO4. The brown/red solution was filtered and dried under reduced pressure and in vacuo to yield an red brown oil that was dried at the high vac. Crude NMR looked promising. Decided to purify to aid next step.

First purification using Biotage Isolera DCM/MeOH 1-10% gradient. Problem with column/solvent pump - failed to elute. washed off column and resubmitted to conditions. Mixture of spots major product: NMR showed product plus impurities. Attempted TLCs in other solvent systems (EtOAc and DCM/Acetone) and found no good separation so submitted crude to AEW 247-2.


Data:

 

AEW 246-2 crude.pdf
AEW 246-2 crude.zip
AEW 246-2 purified 200 mHz.pdf
AEW 246-2 purified.zip

Hazard and Risk Assessment:


Strings:

ClC1=CN=CC2=NN=C(C3CN(CCC3)C(OC(C)(C)C)=O)N21

and

OCC(OC1OCCCC1)C2=CC=CC=C2

to

CC(OC(N(CCC1)CC1C2=NN=C3N2C(OCC(OC4OCCCC4)C5=CC=CC=C5)=CN=C3)=O)(C)C

InChI=1S/C15H20ClN5O2/c1-15(2,3)23-14(22)20-6-4-5-10(9-20)13-19-18-12-8-17-7-11(16)21(12)13/h7-8,10H,4-6,9H2,1-3H3

and

InChI=1S/C13H18O3/c14-10-12(11-6-2-1-3-7-11)16-13-8-4-5-9-15-13/h1-3,6-7,12-14H,4-5,8-10H2

to

InChI=1S/C28H37N5O5/c1-28(2,3)38-27(34)32-14-9-12-21(18-32)26-31-30-23-16-29-17-24(33(23)26)36-19-22(20-10-5-4-6-11-20)37-25-13-7-8-15-35-25/h4-6,10-11,16-17,21-22,25H,7-9,12-15,18-19H2,1-3H3

Attached Files
29th October 2015 @ 03:37

 

 

 

 

Procedure:

 

Hazard and Risk Assessment:


AEW 260-1 frac 1 dmso.pdf


Strings:

InChI=1S/C20H22F2N4O4/c1-13(29-18-4-2-3-9-27-18)12-28-17-11-23-10-16-24-25-19(26(16)17)14-5-7-15(8-6-14)30-20(21)22/h5-8,10-11,13,18,20H,2-4,9,12H2,1H3

to

InChI=1S/C15H14F2N4O3/c1-9(22)8-23-13-7-18-6-12-19-20-14(21(12)13)10-2-4-11(5-3-10)24-15(16)17/h2-7,9,15,22H,8H2,1H3

FC(F)OC(C=C1)=CC=C1C2=NN=C3N2C(OCC(C)OC4OCCCC4)=CN=C3

to

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

Attached Files
16th October 2015 @ 00:48

Procedure:

 

AEW 251-1 (100 mg, 0.318 mmol, 1 equiv.) was stirred in EtOH (3.2 mL) and ammonia (0.300 mL) in a sealed tube and the reaction mixture was stirred at 90 ˚C for 1 h.

Data:

AEW 255-1 crude.zip
AEW 255-1 crude.pdf

Hazard and Risk Assessment:

HIRAC AEW 255-1.pdf
HIRAC AEW 255-1.doc

Strings:

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

to 

NC1=CN=CC2=NN=C(C3=CC=C(OC(F)(F)F)C=C3)N21

InChI=1S/C12H6ClF3N4O/c13-9-5-17-6-10-18-19-11(20(9)10)7-1-3-8(4-2-7)21-12(14,15)16/h1-6H

to

InChI=1S/C12H8F3N5O/c13-12(14,15)21-8-3-1-7(2-4-8)11-19-18-10-6-17-5-9(16)20(10)11/h1-6H,16H2

 

 

 

15th October 2015 @ 04:45

CLogP (ChemDraw): 4.3

 

Procedure:

AEW 205 (200 mg, 0.674 mmol, 1 equiv.), potassium hydroxide (132 mg, 3.26 mmol, 3.5 equiv.) and 18-crown-6 (13 mg, 47.2 μmol, 0.07 equiv.) were stirred in toluene (6.7 mL) and then crude AEW 253-1 (121 mg, 0.674 mmol, 1 equiv.) was added. The reaction mixture was stirred at room temperature and then heated to 40 ˚C for 2h. Still SM.

Water (10 mL) was added and the mixture was extracted with EtOAc (3 x 25 mL). Combined organic layers were washed with water (10 mL), brine (10 mL), dried (MgSO4) filtered and evaporated to give a pale yellow solid (256 mg). 200 MHz NMR recorded.

Ethanol (20 mL) was added to the yellow solid (256 mg) and sonicated (apparent white ppt in yellow solution). Heated with heat gun until gently boiling, ppt remained, allowed to cool to rt and then filtered, washed with ice cold EtOH and dried at the high vac.

 

Data:

2 h, EtOAc

AEW 256-59 TLC #1, 2 h. EtOAc.JPG

AEW 259-1 frac 1 dmso.pdf
AEW 259-1 dmso frac 1.zip

Hazard and Risk Assessment:


Strings:

InChI=1S/C12H7ClF2N4O/c13-9-5-16-6-10-17-18-11(19(9)10)7-1-3-8(4-2-7)20-12(14)15/h1-6,12H

and

InChI=1S/C10H12O3/c1-2-13-10(12)9(11)8-6-4-3-5-7-8/h3-7,9,11H,2H2,1H3

to

InChI=1S/C22H18F2N4O4/c1-2-30-21(29)19(14-6-4-3-5-7-14)32-18-13-25-12-17-26-27-20(28(17)18)15-8-10-16(11-9-15)31-22(23)24/h3-13,19,22H,2H2,1H3

 

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

and

O=C(C(C1=CC=CC=C1)O)OCC

to

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

Attached Files
15th October 2015 @ 04:34

CLogP (ChemDraw): 3.4

 

Procedure:

AEW 205 (200 mg, 0.674 mmol, 1 equiv.), potassium hydroxide (132 mg, 3.26 mmol, 3.5 equiv.) and 18-crown-6 (13 mg, 47.2 μmol, 0.07 equiv.) were stirred in toluene (6.7 mL) and then crude AEW 254-1 (108 mg, 0.674 mmol, 1 equiv.) was added. The reaction mixture was stirred at room temperature and then heated to 40 ˚C for 2h. Still SM.

Water (10 mL) was added and the mixture was extracted with EtOAc (3 x 25 mL). Combined organic layers were washed with water (10 mL), brine (10 mL), dried (MgSO4) filtered and evaporated to give a pale yellow solid (256 mg). 200 MHz NMR recorded.

Ethanol (20 mL) was added to the yellow solid (256 mg) and sonicated (apparent white ppt in yellow solution). Heated with heat gun until gently boiling, ppt remained, allowed to cool to rt and then filtered, washed with ice cold EtOH and dried at the high vac.

 

Data:

2 h, EtOAc

AEW 256-59 TLC #1, 2 h. EtOAc.JPG


Hazard and Risk Assessment:


Strings:

InChI=1S/C12H7ClF2N4O/c13-9-5-16-6-10-17-18-11(19(9)10)7-1-3-8(4-2-7)20-12(14)15/h1-6,12H

and

InChI=1S/C8H16O3/c1-7(6-9)11-8-4-2-3-5-10-8/h7-9H,2-6H2,1H3

to

InChI=1S/C20H22F2N4O4/c1-13(29-18-4-2-3-9-27-18)12-28-17-11-23-10-16-24-25-19(26(16)17)14-5-7-15(8-6-14)30-20(21)22/h5-8,10-11,13,18,20H,2-4,9,12H2,1H3

 

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

and

OCC(OC1OCCCC1)C

to

FC(F)OC(C=C1)=CC=C1C2=NN=C3N2C(OCC(C)OC4OCCCC4)=CN=C3

Attached Files